Oncol Res Treat
43(suppl 1) VII–265 (2020) 43 | S1 | 20 print
ISSN 2296–5270
online
e-ISSN 2296–5262
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e-ISBN 978-3-318-06686-9
ABSTRACTS
Band 43,
Supplement 1,
Februar 2020
online only
34. Deutscher Krebskongress
informativ. innovativ. integrativ.
Optimale Versorgung für alle.
Berlin, 19.–22. Februar 2020
Herausgeber
Andreas Hochhaus, Jena
S. Karger
Medical and Scientific Publishers
Basel
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Inhalt
2018
Index
2018
Deutsche Gesellschaft für Hämatologie und
Medizinische Onkologie e.V.
Österreichische Gesellschaft für
Hämatologie & Medizinische Onkologie
Österreichische Gesellschaft für
Hämatologie & Medizinische Onkologie e.V.
Schweizerische Gesellschaft für Hämatologie
Arbeitsgemeinschaft Internistische Onkologie in
der Deutschen Krebsgesellschaft e. V. (AIO)
Ocial Organ of Editor-in-Chief
M. Hallek, Cologne
Associate Editors
C. Belka, Munich
M. von Bergwelt, Munich
C. Berking, Munich
C. Bokemeyer, Hamburg
M. Borner, Bern
C. Bruns, Cologne
J. Chemmitz, Koblenz
A. Drzezga, Cologne
H.T. Eich, Münster
A. Engert, Cologne
Y. Erim, Erlangen
M. Essler, Bonn
A. Heidenreich, Cologne
M. Hentrich, Munich
R.-D. Hofheinz, Mannheim
W. Janni, Ulm
K. Jordan, Heidelberg
J.P. Klussmann, Cologne
M. Kroiss, Würzburg
A.A. Lammertsma, Amsterdam
H. Lang, Mainz
M. Moehler, Mainz
V. Müller, Hamburg
K. Oechsle, Hamburg
C.P. Pallasch, Cologne
P. Reichardt, Berlin
G. Reifenberger, Düsseldorf
A. Reinacher-Schick, Bochum
M. Schlaeppi, St. Gallen
M. Schmidt, Mainz
M. Schuler, Essen
M. Theobald, Mainz
M. Thomas, Heidelberg
S. Eckhardt (1978–1989), R. Gross (1978–1980), J.H. Holzner (1978–1990), N. Jaeger (1978–1980),
K. Munk (1978–1980), G.P. Murphy 1978–1980), J.P. Obrecht (1978–1979), A. Stacher (1978–1980),
St. Tanneberger (1978–1980), W. Wilmanns (1978–1980), H. Wrba (1978–1980), G.A. Nagel (1981–1988),
W. Queißer (1989–2002), W. Huber (1992–1998), H.-J. Schmoll (2002–2012)
U. Wedding, Jena
W. Wick, Heidelberg
Editorial Board
P. Albers, Düsseldorf
D. Arnold, Hamburg
A. Atmaca, Frankfurt
C. Bausewein, Munich
D. Beutner, Göttingen
P. Brossart, Bonn
E. Dippel, Ludwigshafen
M. Fassnacht, Würzburg
F. Geiser, Bonn
U. Herrlinger, Bonn
A. Hochhaus, Jena
F. Honecker, St. Gallen
H. Kölbl, Vienna
W. Kuhn, Bonn
T. Langer, Lübeck
P. Mallmann, Cologne
D. Marmé, Freiburg i.Br.
A. Mehnert-Theuerkauf, Leipzig
H. Moch, Zurich
I. Runnebaum, Jena
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P. Schöffski, Leuven
F. Schütz, Heidelberg
J. Sehouli, Berlin
N. Skoetz, Cologne
C. Spitzweg, Munich
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S. Ugurel, Essen
R. Voltz, Cologne
M. Weller, Zurich
J. Werner, Munich
T. Zander, Cologne
O. Zivanovic, New York, NY
Member of Deutsche Krebsgesellschaft e.V.
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Disclosure Statement
The Editor declares that he has no conict of interest.
Impressum
Inhalt
2018
Index
2018
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Inhalt
2018
Index
2018
Band 43,
Supplement 1,
Februar 2020
online only
Herausgeber
Andreas Hochhaus, Jena
Supplement 1/2020
e-ISBN 978-3-318-06686-9
Basel . Freiburg . Hartford . Oxford . Bangkok . Dubai . Kuala Lumpur .
Melbourne . Mexico City . Moscow . New Delhi . Paris . Shanghai . Tokyo
34. Deutscher Krebskongress
informativ. innovativ. integrativ.
Optimale Versorgung für alle.
Berlin, 19. 22. Februar 2020
ABSTRACTS
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Oncol Res Treat 2020;43(suppl 1):IV
Kongresspräsident Prof. Dr. Andreas Hochhaus (Jena)
Kongresssekretäre Dr. Tobias Rachow (Jena)
Dr. Philipp Ernst; M.Sc. (Jena)
Dr. Ulrike Laubscher (Jena)
Svetlana Scherübl (Jena)
Gutachter Gerhard Adam (Hamburg); Hojjat Ahmadzadehfar (Bonn); Hakan Alakus (Köln); Udo
Altmann (Gießen); Dirk Arnold (Hamburg); Ulli Simone Bankstahl (Frankfurt/M.);
Sebastian Bauer (Essen); Freerk Baumann (Köln); Jürgen Christian Becker
(Heidelberg); Carola Berking (München); Carsten Bokemeyer (Hamburg); Kerstin
Bornemann (Göttingen); Thomas Brabletz (Erlangen); Jens Büntzel (Nordhausen)
Reinhard Büttner (Köln); Gamze Damnali (Landhut); Maike de Wit (Berlin); Thomas
Decker (Ravensburg Carsten Denkert (Marburg); Andreas Dinkel (München);
Wilfried Eberhardt (Essen); Matthias Ebert (Mannheim); Nadja Ebert (Heidelberg);
Franziska Eckert (Tübingen); Rainer Engers (Neuss); Thomas Ernst (Jena); Philipp
Ernst (Jena); Emmanouil Fokas (Frankfurt/M.); Annette Freidank (Fulda); Simone
Fulda (Frankfurt/M.); Deniz Gencer (Mannheim); Michael Ghadimi (Göttingen); Ines
Gockel (Leipzig); Thorsten Götze (Frankfurt/M.); Paul Graf La Rosée (Villingen-
Schwenningen); Marc-Oliver Grimm (Jena); Christian Grohé (Berlin); Thomas
Gronau (Bendorf); Viktor Grünwald (Essen); Orlando Guntinas-Lichius (Jena); Ralf
Gutzmer (Hannover); Christian Habermann (Hamburg); Andreas Hochhaus (Jena);
Jens Ho󰀨mann (Berlin); Jürgen Ho󰀨mann (Heidelberg); Wilfried Ho󰀨mann
(Badenweiler); Wolfgang Ho󰀨mann (Greifswald); Ralf-Dieter Hofheinz (Mannheim);
Wolf-Karsten Hofmann (Mannheim); Uta Höpken (Berlin); Lars-Christian Horn
(Leipzig); Markus Horneber (Nürnberg); Gerdt Hübner (Oldenburg); Jutta Hübner
(Jena); Christian Jackisch (O󰀨enbach); Klaus-Peter Janssen (München); Karin
Jordan (Heidelberg); Meinolf Karthaus (München); Christian Keinki (Jena); Jens
Peter Klußmann (Köln); Gabi Knötgen (Aurich); Alfred Königsrainer (Tübingen);
Mechthild Krause (Dresden); Matthias Kroiss (Würzburg); Thomas W. Kubin
(Traunstein); Sherko Kümmel (Essen); Annette Lebeau (Hamburg); Hartmut Link
(Kaiserslautern); Diana Lüftner (Berlin); Christian Mawrin (Magdeburg); Anja
Mehnert-Theuerkauf (Leipzig); Susanne Merkel (Erlangen); Oliver Micke (Bielefeld);
Matthias Naegele (Zürich); Jens Neumann (München); Petra Ortner (München);
Friedrich Overkamp (Hamburg); Thorsten Persigehl (Köln); Uwe Platzbecker
(Leipzig); Franz-Josef Prott (Wiesbaden); Tobias Rachow (Jena); Martin Reck
(Großhansdorf); Christian Reinhardt (Köln); Oliver Rick (Bad Wildungen); Anja Rinke
(Marburg); Christoph Ritter (Greifswald); Andreas Rosenwald (Würzburg); Amir
Sabet (Frankfurt/M.); Uwe Schlegel (Bochum); Harald Schmalenberg (Dresden);
Thorsten Schmidt (Kiel); Tilman Schöning (Freiburg); Jalid Sehouli (Berlin); Christine
Sers (Berlin); Thomas Seu󰀨erlein (Ulm); Thorsten Simon (Köln); Marianne Sinn
(Hamburg); Jens Siveke (Essen); Sigrun Smola (Homburg); Christine Spitzweg
(München); Annette Stäbler (Tübingen); Monika Steimann (Boltenhagen); Joachim
P. Steinbach (Frankfurt/M.); Konrad Steinestel (Ulm); Sebastian Stintzing (Berlin);
Andrea Tannapfel (Bochum); Michael Thomas (Heidelberg); Peter Thuss-Patience
(Berlin); Amanda Tufman (München); Beate Volkmer (Buxtehude); Marie von
Lilienfeld-Toal (Jena); Arend von Stackelberg (Berlin); Cornelius Waller (Freiburg);
Stefanie Walter (Bonn); Eva Wardelmann (Münster); Ulrich Wedding (Jena);
Wolfgang Wick (Heidelberg); Elisabeth Wiesmüller (Ulm); Olaf Witt (Heidelberg);
Andrea Wittig Jena Barbara Wollenberg (Lübeck); Tanja Zimmermann (Hannover);
Johannes Zuber (Wien)
Inhalt
2018
Index
2018
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Oncol Res Treat 2020;43(suppl 1):V
Inhalt
Best-of-Abstracts-Vorträge
Basic Research 1
Developmental Therapeutics: Immunotherapy/Cellular Therapy 39
Developmental Therapeutics: Molecular Therapeutics 42
Gastrointestinal (Colorectal) Cancer 47
Gastrointestinal (Noncolorectal) Cancer 58
Genito-urinary Cancer, including Prostate Cancer 69
Gynecological Cancer 87
Leukemia, Myelodysplasia, Transplantation 104
Translational Oncology 197
Other Topics 204
Vorträge
Breast Cancer 6
Cancer Prevention 28
Developmental Therapeutics: Immunotherapy/Cellular Therapy 39
Gastrointestinal (Colorectal) Cancer 47
Gastrointestinal (Noncolorectal) Cancer 58
Genito-urinary Cancer, including Prostate Cancer 69
Gynecological Cancer 87
Head and Neck Cancer 95
Health Economy/Public Health 101
Lymphoma and Plasma Cell Disorders 127
Radiation 161
Rehabilitation and Long-term Burden in Social Medicine (Survivor) 166
Supportive Care 178
Inhalt
2018
Index
2018
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Inhalt
Poster
Basic Research 1
Breast Cancer 6
Cancer Prevention 28
Central Nervous System Tumors 31
Developmental Therapeutics: Cytotoxic Chemotherapy 38
Developmental Therapeutics: Immunotherapy/Cellular Therapy 39
Developmental Therapeutics: Molecular Therapeutics 42
Endocrine Tumor (e.g. Thyroid Cancer, Adrenal Tumor, Neuroendocrine Tumor) 43
Epidemiology 44
Gastrointestinal (Colorectal) Cancer 47
Gastrointestinal (Noncolorectal) Cancer 58
Genito-urinary Cancer, including Prostate Cancer 69
Geriatric Oncology 84
Gynecological Cancer 87
Head and Neck Cancer 95
Health Economy/Public Health 101
Imaging 103
Leukemia, Myelodysplasia, Transplantation 104
Lung Cancer 110
Lymphoma and Plasma Cell Disorders 127
Molecular Pathology 134
Novel Agents/Early Clinical Trials 135
Oncological Pharmacy 137
Pediatric Cancer 138
Palliative Care 139
Pege 142
Psychooncology 145
Quality of Life 153
Radiation 161
Rehabilitation and Long-term Burden in Social Medicine (Survivor) 166
Sarcoma 171
Skin Cancer, including Melanoma 174
Supportive Care 178
Surgical Oncology 192
Translational Oncology 197
Other Topics 204
Inhalt
2018
Index
2018
Oncol Res Treat 2020;43(suppl 1):VI
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Inhalt
Late-Breaking Abstracts
Vorträge
Cancer Prevention 211
Developmental Therapeutics: Immunotherapy/Cellular Therapy 213
Gastrointestinal (Colorectal) Cancer 218
Gastrointestinal (Noncolorectal) Cancer 220
Head and Neck Cancer 230
Lung Cancer 232
Lymphoma and Plasma Cell Disorders 238
Poster
Breast Cancer 209
Cancer Prevention 211
Central Nervous System Tumors 212
Developmental Therapeutics: Cytotoxic Chemotherapy 213
Developmental Therapeutics: Molecular Therapeutics 216
Epidemiology 218
Gastrointestinal (Colorectal) Cancer 218
Gastrointestinal (Noncolorectal) Cancer 220
Genito-urinary Cancer, including Prostate Cancer 224
Geriatric Oncology 227
Head and Neck Cancer 230
Immunotherapy Side Eects 231
Lung Cancer 232
Pediatric Cancer 238
Palliative Care 240
Psychooncology 240
Radiation 242
Rehabilitation and Long-term Burden in Social Medicine (Survivor) 242
Sarcoma 243
Skin Cancer, including Melanoma 243
Supportive Care 244
Autorenindex 247
Impressum II
Oncol Res Treat 2020;43(suppl 1):VII
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Abstracts
Inhalt
2018
Index
2018
© 2020 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/ort
Basic Research
Best-of-Abstracts-Vorträge
528
The Oncogenic MDm4 Protein acts as a Supporter
of DNA-Replication
Kai Wohlberedt 1; Ina Klusmann 1; Polina Derevyanko 1;
Valentina Manzini 1; Celeste Giansanti 1; Josephine Choo 1;
Anna Magerhans 1; Christine Eischen 2; Aart Jochemsen 3;
Matthias Dobbelstein 1
1Institute of Molecular Oncology, University Medical Center Göttingen,
Deutschland
2Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas
Jeerson University Philadelphia, United States
3Department Cell and Chemical Biology, Leiden University Medical Center,
Niederlande
Purpose: e Mdm4 (alias Mdmx) oncoprotein heterodimerizes with
Mdm2 and together they antagonize the tumor suppressor p53. p53-inde-
pendent activities of the two Mdm proteins are emerging, and we have re-
ported the ability of Mdm2 to modify chromatin [1] and to support DNA
replication by suppressing the formation of DNA/RNA hybrids (R-loops)
[2]. We asked whether Mdm4 can also contribute to an unperturbed DNA
replication fork progression.
Methods: Quantication of the speed and processivity of single DNA rep-
lication forks in tumor-derived as well as non-transformed cell lines was
assessed by DNA ber assays upon removal of Mdm4. Immunoblots and
immunouorescence microscopy allowed us to determine indicators of
replicative stress. Cell proliferation assays and cytometry following EdU
incorporation were used to investigate cell survival and overall DNA syn-
thesis.
Results: e loss of Mdm4 in p53-decient cells strongly impaired DNA
replication fork progression. Co-depletion of Mdm4 and Mdm2 com-
promised DNA replication even further, arguing that they act through
partially distinct mechanisms. Further analysis revealed that the RING
domain of Mdm4 was necessary to ensure DNA replication fork pro-
gression. By inducing the formation of DNA/RNA hybrids, Mdm4 de-
pletion signicantly increased replication stress. Due to elevated ring of
replication origins, loss of Mdm4 only marginally aected cell prolifera-
tion but sensitized p53-/- cells to the nucleoside analogue gemcitabine.
Conclusions: Mdm4 supports DNA replication by preventing the ac-
cumulation of DNA/RNA hybrids independent of p53. ese ndings
suggest a new route of chemosensitization with low toxicity using Mdm4
inhibitors and further support Mdm4 as a therapeutic target in cancer.
References:
1. Wienken et al., Molecular Cell 2016
2. Klusmann et al., PNAS 2018
Disclosure Statement: e authors declare no conict of interest.
Poster
146
Dierences in Mitochondria between Normal and Cancer Cells
as Molecular Cancer Target
Alexander Gosslau
City University of New York, Department of Biology, New York, United States
Purpose: Cancer prevention therapies with an induction of apoptosis in
cancer cells with least adverse eects on normal cells is a particularly de-
sirable strategy in cancer research.
Methods: Fluorescence, transmission and scanning electron microscopy,
Immunohistochemistry, RT-PCR, Western Blot analysis.
Results: We demonstrated that a matched pair of isogenetic normal
and transformed counterpart cells (WI38/WI38VA) showed a selective
induction of the mitochondrial-mediated apoptotic pathway only in
tumor but not in normal cells in response to resveratrol analogs, black tea-
derived theaavins, and oxidative stress. Tumor cells bearing a bubble-like
mitochondrial network showed intrinsic apoptosis in response to various
inducers. In contrast, normal counterpart cells or tumor cells which
were resistant to apoptosis were composed of a web-like mitochondrial
reticulum.
Conclusions: In summary, our results indicate a correlation between
mitochondrial morphology and the capacity for induction of apoptosis.
Knowledge about mitochondrial morphology or cellular components
impacting mitochondria (e.g. microtubule) thus oer a unique molecu-
lar site against which selective natural-derived bioactives and/or physi-
co-chemical inducers might be targeted.
Relevant References:
1. Gosslau, A., Pabbaraja, S., Knapp, S., and Chen, K.Y. (2008) Trans- and
cis-stilbene polyphenol derivatives induced rapid perinuclear mitochondrial
clustering and p53-independent apoptosis in cancer cells but not normal cells.
Eur. J. Pharmacol., 587, 25-34
2. Gosslau, A., and Chen, K.Y. (2004) Nutraceuticals, apoptosis, and disease
prevention. Nutrition 20, 95-102 (Review)
Disclosure Statement:
Relevant nancial relationships:
Professor, Dept. of Science (Biology), City University of New York, BMCC
Relevant non-nancial relationships:
Visiting Professor, Dept. of Food Science, Rutgers University, New Brunswick,
New Jersey
Editorial Board member, Movement and Nutrition in Health and Disease
Associate Editor-in-Chief, Food Science and Human Wellness
Oncol Res Treat 2020;43(suppl 1):1–265
DOI: 10.1159/000506491
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts2
Inhalt
2018
Index
2018
443
Mechanisms of Mitigating Aneuploidy-Induced Telomere
Replication Stress by Telomerase
Sabine Meessen 1; Sebastian Iben 2; Anca Azoitei 1; Sebastian Wiese 3;
Christian Bolenz 4; Cagatay Günes 1
1Urologie und Kinderurologie, Universitätklinikum Ulm, Ulm, Deutschland
2Dermatologie und Allergologie, Universitätsklinikum Ulm , Ulm
3Core Unit Mass Spectrometry an Proteomics, Universitätsklinikum Ulm, Ulm
4Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Ulm,
Deutschland
Purpose: Aneuploidy represents a hallmark feature of carcinogenesis in
humans but mutations in the canonical ploidy-control genes are rare as
these mutations impair cell tness. Recent data indicate that aneuploidy
can inhibit or instigate tumorigenesis dependent on the genetic back-
ground. ese observations imply that aneuploidy can be induced by
non-canonical ploidy-control mechanisms and tumor cells activate mech-
anisms to allow survival of aneuploid cells. We have recently identied
non-canonical ploidy-control genes and could show that telomerase rep-
resents an aneuploidy survival mechanism. We aim to elucidate the path-
ways of canonical and non-canonical aneuploidy induction and the mech-
anisms how telomerase suppresses aneuploidy-induced cell senescence.
Methods: Knockdown or knockout of MAD2 (canonical ploidy-control
gene) or ORP3 (non-canonical ploidy control gene) is achieved in telo-
merase positive and telomerase negative human broblasts by shRNAs or
the CRISPR-Cas9 technology. e replication stress is evaluated by immu-
nouorescence staining of p-RPA2, an established marker for replication
stress. We further use proteome analyses to answer the question whether
telomerase itself is sucient to suppress aneuploidy-induced replication
stress or whether it requires cooperation partners for this process.
Results: e knockdown and knockout of ORP3 induces aneuploidy in
both, telomerase negative and positive cells. As reported previously, aneu-
ploidy induction resulted in increased replication stress and impairment
of cell proliferation in telomerase negative primary human broblasts (BJ)
while ectopic expression of telomerase in these cells (BJ-hTERT) sup-
presses aneuploidy-induced replication stress. Initial results indicate the
involvement of helicases mitigating aneuploidy-induced replication stress
and to allow continuous proliferation of aneuploid cells.
Conclusions: e data indicate that telomerase requires cooperation
partners, such as helicases, to suppress to suppress aneuploidy-induced
replication stress.
449
Identication of Microvesicle-Specic Proteins and their
Implications in Vesicle Biogenesis
Cedric Weich 1; Leon Kaiser 2; Matthias Schulz 2; Hanibal Bohnenberger 3;
Christof Lenz 4; Claudia Binder 2; Annalen Bleckmann 1, 2; Kerstin Menck 1, 2
1Universitätsklinikum Münster, Medizinische Klinik A, Münster, Deutschland
2Universitätsmedizin Göttingen, Klinik für Hämatologie/Medizinische
Onkologie, Göttingen, Deutschland
3Universitätsmedizin Göttingen, Institut für Pathologie, Göttingen, Deutschland
4Universitätsmedizin Göttingen, Institut für Klinische Chemie, Göttingen,
Deutschland
Purpose: Extracellular vesicles are increasingly recognized as important
mediators of intercellular communication and biomarkers in cancer. ey
are divided into two main populations, the small exosomes (Exo, diame-
ter <150 nm) that derive from multivesicular endosomes, and larger mi-
crovesicles (MV, diameter 100-1000 nm) that bud o directly from the
cell membrane. While key regulators of Exo secretion have been recently
identied, the biogenesis of MV is barely understood. erefore, the aim
of this study was to identify novel MV proteins that might play a role in
MV biogenesis.
Methods: We isolated MV and Exo from SK-BR-3 breast cancer cells and
used SILAC (stable isotope labeling by/with amino acids in cell culture)
followed by mass spectrometry to compare their proteome. MV-specic
proteins were validated by Western Blot and analyzed for their eect on
MV biogenesis.
Results: Comparison of the MV and Exo proteome revealed 171 proteins
to be signicantly dierentially expressed, among them many proteins as-
sociated with cytoskeletal organization that were exclusively present on
MV. We validated the expression of these proteins on MV and Exo from
several breast cancer as well as normal cell lines and showed that Rgap1,
Prc1 and Kif4a were indeed expressed specically on MV from all cells.
Knockdown of these proteins by siRNA in SK-BR-3 cells and subsequent
analysis of their secreted vesicles by Western Blot and Nanoparticle Track-
ing Analysis suggested that the three proteins were indeed involved in MV
biogenesis. Interestingly, all three proteins are associated with microtu-
bules and play an important role in cytokinesis. erefore, our ongoing
research focuses on analyzing the intracellular expression and co-localiza-
tion of the identied markers with other known MV-specic proteins as
well as studying the inuence of microtubule inhibitors on MV biogenesis.
Conclusions: Taken together, our results identied 3 novel regulators of
MV biogenesis and suggest that microtubules are involved in this process.
Disclosure Statement: e authors have nothing to disclose.
459
The Non-Canonical WNT Ligand-Receptor Pair WNT11/
ROR2 Mediates Breast Cancer Invasion through RHOA/ROCK
Signaling
Kerstin Menck 1, 2; Saskia Heinrichs 1, 2; Maren Sitte 3; Tim Beissbarth 3;
Helen Noeding 4; Andreas Jansho 4; Claudia Binder 2;
Annalen Bleckmann 1, 2
1Universitätsklinikum Münster, Medizinische Klinik A, Münster, Deutschland
2Universitätsmedizin Göttingen, Klinik für Hämatologie/Med. Onkologie,
Göttingen, Deutschland
3Universitätsmedizin Göttingen, Institut für Medizinische Bioinformatik,
Göttingen, Deutschland
4Georg-August-Universität Göttingen, Institut für Physikalische Chemie,
Göttingen, Deutschland
Purpose: Breast cancer (BC) is the second most common tumor entity
worldwide. Tumor progression leads to the formation of metastases for
which there is still no curative therapy. Several studies have suggested that
BC metastasis involves activation of the Wnt pathway. In this study we
aimed to identify novel pathways members involved in BC progression.
Methods: Gene expression data from BC patients were analyzed for
the expression of Wnt proteins associated with metastasis. Candidate
proteins were modulated for their expression in cell lines and their role
in tumor progression was analyzed by functional assays and molecular
characterization.
Results: Using a targeted analysis of gene expression data from BC pri-
mary tumors and metastases, we found that especially the β-catenin inde-
pendent, non-canonical Wnt signaling pathway is active in metastases and
associated with poor survival. In particular the non-canonical Wnt recep-
tor Ror2 was found to be highly expressed in BC brain metastases and was
associated with worse metastasis-free survival. To understand the molec-
ular basis for these observations, we overexpressed Ror2 in human BC cell
lines which led to an increase in tumor invasion that was dependent on
increased RhoA and Rock expression. Ror2-overexpressing cells showed
defects in cell morphology and cell-cell contacts in microscopic assays as
well as Electric Cell-Substrate Impedance Sensing (ECIS) measurements.
In order to identify the ligand responsible for these changes, cells were
characterized by RNA-Seq and real-time PCR which revealed an upregu-
lation of the non-canonical Wnt11 ligand. Co-immunoprecipitation con-
rmed that Wnt11 acted as a novel ligand for Ror2. Wnt11 activated Rock
signaling and its knockdown reversed the pro-invasive phenotype and
changes in Ror2-overexpressing cells. High Wnt11 levels in primary BC
patient samples were associated with poor metastasis-free survival.
Conclusions: Our study has revealed Wnt11/Ror2 as a novel target driv-
ing tumor invasion and progression in BC.
Disclosure Statement: e authors have nothing to disclose.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 3
Inhalt
2018
Index
2018
526
CXCR4LASP1 Interaction – Dierences between Breast
Cancer and CML
Jochen Frietsch 1; Andreas Herrmann 2; Cristina Peperina Viciano 3;
Andreas Hochhaus 1; Thomas Ernst 1; Carsten Homann 4; Alma Zernecke 2;
Elke Butt 2
1Universitätsklinikum Jena, Klinik für Innere Medizin II, Abteilung für
Hämatologie und Internistische Onkologie, Jena, Deutschland
2Universitätsklinikum Würzburg, Institut für Experimentelle Biomedizin II
Würzburg
3Universitätsklinikum Würzburg, Rudolf-Virchow-Zentrum für Experimentelle
Biomedizin, Würzburg
4Universitätsklinikum Jena, Institut für Molekulare Zellbiologie, Jena
Purpose: CXCR4 has been reported to play an important role in cell sur-
vival, proliferation, migration, as well as metastasis of tumors. Activation
by SDF-1 activates PI3K/AKT signaling. In breast cancer (BC), overex-
pression of CXCR4 is involved in directing metastasis of CXCR4 positive
tumor cells to organs producing SDF-1. In CML, CXCR4 is down-regulat-
ed by BCRABL causing defective adhesion of CML cells to bone marrow
stroma.
Recently, the cytoskeletal and adaptor protein LASP1 was described as a
novel CXCR4 binding partner and a promoter of the PI3K/AKT pathway.
We sought to investigate the LASP1-CXCR4 axis in solid and hematopoi-
etic malignancy and propose a model in which both signaling pathways
are interconnected.
Methods: MDAMB-231 BC and K562 CML cells were used to investigate
the phosphorylation-dependent dierences in binding of LASP1 to CXCR4
by immunoblotting, pull-down experiments and immunouorescence
staining. Cells with knockdown of CXCR4/LASP1 as well as CXCR4-CFP/
Venus-LASP overexpressing HEK293 cells were employed for probing
CXCR4-LASP1 signaling.
Results: In BC cells, overexpressed LASP1 shows S146 phosphorylation
and nuclear translocation whereas in advanced CML, the protein is down-
regulated and Y171 hyperphosphorylation is observed.
Binding of LASP1 to CXCR4 only occurs aer S146 phosphorylation. e
phosphorylation is transient: Upon CXCR4 stimulation, dephosphoryla-
tion of LASP1 at the PKA-site (S146) and concomitant phosphorylation
at Y171 by TKs occurs. Opposite eects are observed in CXCR4 decient
CML cells treated with TKI to block BCR-ABL.
Conclusions: In BC cells, binding of pLASP1-S146 stabilizes the C-tail
of the CXCR4 and hinders the phosphorylation at multiple PKC serine
phosphorylation sites important for receptor internalization. In contrast,
increased LASP1-Y171 phosphorylation by BCR-ABL renders the protein
less ane to the CXCR4 C-terminus, and facilitates serine and tyrosine
phosphorylation, resulting in down-regulation of CXCR4 and causing de-
fective adhesion of CML cells to bone marrow stroma.
Disclosure Statement: EB and JF have received grants from the German Cancer
Aid (Project numbers: 70112717 and 70112142).
e authors declare no conicts of interests.
551
IL17A+ CD4+ T Cell Heterogeneity in Colorectal Cancer
Leonie Konczalla 1; Filippo Cortesi 1; Tabea Sturmheit 2; Anna Wöstemeier 1;
Jenny Krause 2; Ramez Wahib 1; Jakob R. Izbicki 1; Daniel Perez 1;
Samuel Huber 2; Nicola Gagliani 1, 2
1Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum
Hamburg-Eppendorf , Hamburg , Deutschland
2II. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg ,
Deutschland
Purpose: Recently, cancer therapy has been overturned by the discovery
of immunotherapies targeting co-inhibitory receptors (CIR) as PD-1.
However, in CRC, immunotherapies did not meet the expectations, as
only a minority benet. We hypothesize that two key factors can contrib-
ute to the poor ecacy in CRC: (I) the functional heterogeneity of the
targeted cells and (II) the local microenvironment.
Methods: Human T cell analysis by FACS, RNAseq, TCRseq and CITE-
seq. Functional tests in murine CRC models with dierent microbiota.
In vitro T cell dierentiation by co culture with 3-dimensional primary
tumor structure.
Results: We show accumulation of dierent subsets of IL-17A+ CD4 T
cells in CRC. One subset is characterized by the co-expression of FoxP3,
the key regulator of anti-inammatory T-cells, and of IL-17A, a pro tum-
origenic cytokine. In line, our murine data suggest strong tumor fostering
activity of IL17A+ FoxP3+ CD4 T cells. Importantly, these cells express
several CIR. erefore, they react to immunotherapy, but in an undesir-
able, tumor supporting manner. In addition, tumor progress is modied
by dierent microbiota. Interaction of CD4 T cells and the microbiome is
of pivotal importance in directing immune response 1. Interestingly, there
is evidence that the microbiota composition impacts the success or failure
of immunotherapy 2. If the microbiota modulates IL-17A+ FoxP3+ CD4
T cell abundance and their CIR pattern needs to be claried. is might
determine the ecacy of immunotherapy.
Conclusions: IL17A+ FoxP3+ CD4 T cells are promoting tumor growth
and express several CIR. If these CIR correlates with a special composition
of the colonic microbiome needs to be elucidated. Characterizing this pro
tumorigenic cell population, we seek to determine the best immunother-
apy regimen for CRC patients.
References:
1. Ivanov, II, et al., Induction of intestinal 17 cells by segmented lamentous
bacteria. Cell, 2009. 139(3): p. 485-98.
2. Gopalakrishnan, V., et al., Gut microbiome modulates response to anti-PD-1
immunotherapy in melanoma patients. Science, 2018.
580
Characterization of Tumor Cell-Derived Extracellular Vesicles
in Liquid Biopsies
Fanny Ender 1; Piet Zamzow 1; Nikolas von Bubno 1; Frank Gieseler 1
1Clinic for Hematology and Oncology, UKSH Lübeck, Lübeck, Deutschland
Purpose: Extracellular vesicles (EVs) are released by eukaryotic cells in-
cluding tumor cells1. Due to their small size (< 1 µm), they can be detect-
ed in all body uids. In order to be used as diagnostic markers in liquid
biopsies, EV subpopulations (e.g. exosomes, ectosomes, apoptotic bodies)
need to be detected and characterized. Here, we share our experiences and
give suggestions for technical improvements.
Methods: We used the human pancreatic cancer cell line COLO357 as a
source for EVs. EV subpopulations were separated by sequential centrif-
ugation based on size and mass. Membranes of intact EVs were labeled
with CFSE and analyzed using a high-resolution ow cytometer as well
as nanoparticle tracking analysis (NTA). According to previous publica-
tions, and in accordance with our observations, cells, cellular debris and
apoptotic bodies were pelleted using (2x) 2.500 x g (low speed). en, an
EV sub-fraction was selectively enriched (ectosomes) by 10.000 x g (high
speed). Nevertheless, a sheer separation of ectosomes and exosomes was
not possible due to overlapping sizes.
Results: Subsequently, we optimized staining conditions and adapted
settings for ow cytometry analysis. While 1 µM CFSE was sucient
for membrane labeling of cells, we now recommend a 40-fold higher
concentration for EVs; of note: unlabeled high-speed EVs were
indistinguishable from background noise. Short incubation times and
stable temperature conditions were of major importance for yielding
intact vesicles. Most important, threshold adjustment of uorescence
channel aected the resolution of CFSE-labeled EVs and thus, signicantly
inuenced EV quantication.
Conclusions: Liquid biopsies embody the future of precision medicine in
oncology. Protocol optimization and standardization for sample collec-
tion, processing and analysis have to be dened precisely for accurate and
comparable results.
Reference:
1. Yáñez-Mó et al., J Extracell Vesicles 2015
Disclosure Statement: e Authors declare no conict of interest.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts4
Inhalt
2018
Index
2018
582
Novel Nanowell-Based Workow for Single Circulating Tumor
Cell Isolation with Cellcelector™
Liwen Yang 1; Mahdi Rivandi 1; André Franken 1; Constantin Nelep 2;
Jens Eberhardt 2; Dieter Niederacher 1; Tanja Fehm 1; Hans Neubauer 1
1Department of Obstetrics and Gynecology, University Hospital of Düsseldorf,
Düsseldorf, Deutschland
2ALS Automated Lab Solutions GmbH, Jena, Deutschland
Purpose: e CellCelector™ system enables the isolation of single circu-
lating tumor cells (CTCs) for comprehensive genomic analysis. However,
although dierent technologies are used to pre-enrich CTCs, high num-
bers of contaminating white blood cells (WBCs) are still impeding single
cell isolation.
In addition, deposition control of isolated CTCs is currently not possi-
ble due to separation of deposition and aspiration areas of CellCelector,
which causes extra costs when empty tubes will be processed e.g. by whole
genome amplication.
We aimed to implement technical solutions to both issues in order to op-
timize and speed-up single cell micromanipulation.
Methods: SKBR3 cells were loaded onto PDMS nano-well chips of dif-
ferent geometries. We tested the size of nano-wells with cavities ranging
from 15µm to 30µm in diameter and determined a) the cell seeding rate
(% of cells captured in nano-wells); b) the cell picking success rate; c) the
cell purity rate (i.e. isolation of the target cell without co-aspiration of cells
in neighbouring well); and d) on chips staining recover rate. Deposition
was veried by microscopic inspection with at bottom tubes. Validation
experiments were done with the patients CellSearch sample.
Results: Best cell seeding rates were observed with 30µm nano-wells, with
15µm nano-wells many cells were not captured. e experiments using
30µm wells of dierent geometries are in progress. On-chip staining re-
sulted in a recovery rate of 80%-90%. Deposition control worked to 100%
with 4titudes at bottom tubes. A new adapter for CellCelector was de-
signed and produced to execute this workow on the microscope stage
thereby also increasing the speed of micromanipulation by approx. 50%
to 60%.
Conclusions: We have improved single CTCs isolation with the CellCe-
lector by implementing nano-well chips for cell separation and at bottom
tubes to control cell deposition. Apart from the reduced processing time
this will also reduce the costs caused by unsuccessful cell deposition.
648
Low Dose Irradiation Stimulates Spherogenesis via
Alterations in Cytokine Secretion
Marise Walter-Diessars 1; Diana Freitag 1; Werner Dammermann 2;
Lukas Hain 1; Nasrin Abbasi-Senger 3; Tilo Wiezorek 3; Andrea Wittig 3;
Rolf Kal 1; Jan Walter 1,4
1University Hospital Jena, Department of Neurosurgery, Jena, Deutschland
2University Hospital Brandenburg- Brandenburg Medical School, Center of
Internal Medicine II, Brandenburg, Deutschland
3University Hospital Jena, Department of Radiotherapy and Radiation Oncology,
Jena, Deutschland
4Medical Center Saarbruecken, Department of Neurosurgery, Saarbrücken,
Deutschland
Purpose: Ionizing radiation is a known risk factor for the development of
meningiomas. However, the underlying mechanism is largely unknown. It
is discussed whether radiation triggers mutations or (immuno-)modula-
tory processes, that might lead to the dedierentiation of somatic cells and
ultimately to the development of tumor stem cells. e aim of this study
was to investigate the inuence of ionizing radiation on immunomodu-
latory processes in meningioma cells (PMCs) and non-pathological dura
mater cells (DMCs) in vitro.
Methods: ree PMC and three DMC cultures were cultivated under
standard conditions. e conuent monolayers were exposed to a single
dose of photon irradiation (1, 2, 4, 8, 12, 16, 20 Gy). 24h and 7, 14, 21 and
28 days aer treatment, cells were passed and analyzed. Analyses were
performed in respect to morphology (cell shape, generation times, etc.),
molecular biology and immunological aspects .
Results: In the high-dose radiation group (>= 8Gy) morphological anal-
yses showed clear signs of necrosis in all cell types. Under certain condi-
tions all cell types showed a tendency to detach from the subsurface, and
low-dose irradiated cells (<= 4Gy) tended to form spheroids. Compared
to DMS, in PMCs this eect was seen later (7d vs. 21d). In addition, 28d
aer irradiation, DMCs were more sensitive to radiation than PMCs. It
was found that the equivalent experimental group to the IC50 values de-
termined for each culture was also the group with the highest IL6 secre-
tions aer 28d. Further correlations were found between the time of the
maximum IL6 secretions and the occurrence of spheroids in the PMCs.
e IL8 secretion also showed a relation between the replacement of the
cells at spherogenesis by decreasing concentrations.
Conclusions: Based on the presented data, a correlation between the se-
cretion of IL6+IL8 and the formation of stem cell specic spheroids might
be hypothesized. us, it seems possible that a radiation-induced cytokine
secretion may trigger a stem cell-like phenotype formation.
Disclosure Statement: e authors report no conicts of interest.
649
Dened Glucose Levels Stimulate Metabolic Reprogramming
and Tumor Augmenting Processes in Human Meningioma
Cells
Sophie Huppertz 1; Diana Freitag 1; Undine Tiller 1; Rolf Kal 1; Jan Walter 1, 2
1University Hospital Jena, Department of Neurosurgery, Jena, Deutschland
2Medical Center Saarbruecken, Department of Neurosurgery, Saarbrücken
Purpose: In contrast to normal mammalian cells, cancer cells use glycol-
ysis to generate energy due to their increased metabolism. is eect has
an important role in carcinogenesis and tumor progression. e extent to
which this also applies to meningiomas has not yet been investigated. e
aim of this study is to investigate the inuence of dierent glucose levels
during glycolysis on tumor-promoting processes in human meningiomas.
Methods: e meningioma cell line Ben Men-1 was cultured 24h in a
glucose-free medium. Aerwards, the metabolic activity was measured
by MTT assay and the proliferation rate by BrdU ELISA under 14
dierent glucose concentrations (0 to 100 mM). A peak tting analysis
was used to determine the concentrations for maximum eect in both
assays. Subsequently, 5 concentrations were determined that promote
maximum, minimum and optimal activities. e cells were seeded at a
density of 6x 105 cells/25cm2 and further cultured under the previously
dened conditions. Doubling times, morphological changes and marker
expression were determined by immunocytochemistry.
Results: A maximum of metabolic activity was seen at glucose concen-
trations of 17.2 mM and 66.7 mM, and maximum proliferation rates
at concentrations of 18.5 mM, 35.6 mM and 57.3 mM. Based on these
facts, meningioma cells were then cultured and analyzed with glucose
concentrations of 0, 15, 40, 65 and 100 mM. It was found that long-term
cultivation (>p4) under 15-65 mM glucose was possible. Cells fed with
65 mM glucose showed the fastest doubling times. e IHC characteri-
zation showed surprisingly decreasing vimentin and EMA signals in the
65 mM group in contrast to the other investigation groups. In addition, we
found increased values for pmTOR and GLUT3.
Conclusions: Our results show that meningioma cells also respond to an
increase in environmental glucose levels with an increased tumor progres-
sion. In particular, the increased expression of GLUT3 and p-mTOR sug-
gests a possible metabolic reprogramming in this context.
Disclosure Statement: e authors report no conicts of interest.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 5
Inhalt
2018
Index
2018
662
Irradiation as a Trigger for Cellular Reprogramming of Human
Meningioma Cells
Lukas Hain 1; Diana Freitag 1; Nasrin Abbasi-Senger 2; Tilo Wiezorek 2;
Andrea Wittig 2; Rolf Kal 1; Jan Walter 1, 3
1University Hospital Jena, Department of Neurosurgery, Jena, Deutschland
2University Hospital Jena, Department of Radiotherapy and Radiation Oncology,
Jena, Deutschland
3Medical Center Saarbruecken, Department of Neurosurgery, Saarbrücken,
Deutschland
Purpose: In previous studies it could be shown that irradiation is a de-
cisive risk factor for the development of meningiomas. e underlying
mechanism is still largely unknown. A promising hypothesis is based on
the existence of tumor stem cells expressing embryonic NANOG1 as well
as tumor-specic NANOGP8 at dierent levels. e aim of this study was
to investigate the eects of ionizing radiation on the induction of plurip-
otent stem cells from primary WHO°I meningioma cells (PMC) in vitro.
Methods: ree PMC cultures were incubated under standard conditions
and subsequently exposed to single dose photon irradiation (1, 2, 4, 8, 12,
16, 20 Gy). Aer 24h the cells were rst passed and cultivated for 9 more
passages or 84d. At the end of the experiment the expression of NANOG
(immunocytochemistry) as well as the secretion of the cytokines IL-6 and
IL-8 were analysed. e dierence between NANOG1 and NANOGP8
mRNA expression was determined.
Results: Especially in the low-dose radiation range (1-4 Gy), PMCs
showed a change in morphological properties towards cell clusters and
spheroid cells, which is a well-known property of stem cells. Additionally,
aer low-dose irradiation, PMCs showed a clear tendency towards faster
growth. Immunocytochemistry showed weak NANOG expression in tu-
mor cells. qPCR showed a signicantly higher expression of the NANOG1
gene variant in the 1 Gy (p=0.038), 2 Gy ( p=0.045) and 4 Gy (p=0.005)
radiation group compared to untreated cells. Analysis of NANOGP8
showed no signicant dierences. Additionally, the treated cells showed
an altered, partially stronger secretion of the cytokines IL6 and IL8.
Conclusions: Irradiation aects the proliferation of meningioma cells in
dierent ways and can induce the formation of spheroids in low-dose irra-
diated cultures. In addition, photon exposure leads to a signicantly high-
er expression of embryonic and stem cell associated NANOG1. erefore,
ionizing radiation seems to be a potential factor in cell reprogramming
and thus in tumor development.
Disclosure Statement: e authors report no conicts of interest.
689
Hepatocyte-Specific Deletion of mTOR Accelerates Colorectal
Liver Metastasis
Long Jiao 1; Roman Eickho 2; Athanassios Fragoulis 2; Ulf Peter Neumann 2;
Thorsten Cramer 2
1Surgery, RWTH University Aachen, Aachen, Deutschland
2RWTH Aachen University Hospital, RWTH University Aachen, Aachen,
Deutschland
Purpose: e mTOR protein is of central importance for the regulation
of cell proliferation, metabolism and autophagy. Activation of the mTOR
pathway is frequently found in cancer, resulting in the notion that tar-
geting mTOR represents a useful approach for cancer therapy. Of note,
mTOR inhibitors have thus far failed to demonstrate signicant antipro-
liferative ecacy in the majority of cancer types. It is therefore of pivot-
al importance to better understand the functional signicance of mTOR
inhibition for the pathogenesis of cancer. We sought to characterize the
cell type-specic role of mTOR for the pathogenesis of colorectal liver
metastases.
Methods: We established a liver epithelial cell (LEC)-specic knock-out
(KO) of mTOR via the Cre/loxP-system (termed mTORLEC mice) and char-
acterized the growth of colorectal liver metastases (CRLM) in mTORLEC
mice compared to wildtype (WT) controls.
Results: Unexpectedly, tumor nodules in the CRLM model were signi-
cantly larger in mTORLEC mice compared to controls. We hypothesized
that the KO of mTOR in LECs resulted in the formation of a pro-tum-
origenic microenvironment in the liver. To further analyze this, we de-
termined the expression of pro-inammatory factors in WT versus KO
livers. While the expression of COX-2, HIF-1α, TNF-α and IL-6 was not
aected, IL-1β gene expression was found to be signicantly higher in the
livers of mTORLEC mice. Furthermore, mTORLEC mice displayed peripor-
tal leukocyte accumulation that was absent in livers from WT mice. e
functional relevance of this nding for the accelerated metastasis forma-
tion in mTORLEC mice is currently being evaluated by us.
Conclusions: We show an unexpected acceleration of liver metastases
upon functional deletion of mTOR specically in liver epithelial cells.
Our results add a further layer of complexity to the biology of mTOR and
suggest that cell and tissue type-specic factors need to be considered in
order to comprehend the role of mTOR for tumor biology.
Disclosure Statement: none
757
PGRMC1 Alters de Novo Lipid Biosynthesis Resulting
in Enhanced Oncogenic Signaling
Nadia Stamm 1; Hannah Asperger 1; Marina Ludescher 1; Tanja Fehm 1;
Hans Neubauer 2
1Klinik für Geburtshilfe und Frauenheilkunde, Universitätsklinikum Düsseldorf,
Forschungslabor, Düsseldorf, Deutschland
2Klinik für Geburtshilfe und Frauenheilkunde, Universitätsklinikum Düsseldorf,
Düsseldorf, Deutschland
Purpose: Progesterone Receptor Membrane Component-1 (PGRMC1) is
upregulated in breast cancers and is associated with a worse survival in
breast cancer patients. In the present study we describe a potential mecha-
nism by which PGRMC1 potentially contributes to breast cancer progres-
sion through deregulation of cholesterol and lipid homeostasis, leading to
enhanced oncogenic signaling.
Methods: PGRMC1 interaction partners were identied by co-immuno-
precipitation followed by mass spectrometry and validated using proxim-
ity ligation assay (PLA) in various breast cancer cell lines. To study how
elevated PGRMC1 expression contributes to cholesterol homeostasis, we
determined levels of cholesterol and estradiol in PGRMC1 overexpressing
breast cancer cells and investigated sensitivity to statin treatment. Addi-
tionally, we determined the activity of estrogen receptor (ERα) at condi-
tions of PGRMC1 overexpression and downregulation.
Results: PGRMC1 overexpression resulted in increased proliferation rates
in cell culture and in signicantly increased tumor volume in xenogra
models. PGRMC1 was further found to interact with proteins involved
in cholesterol and lipid synthesis. Overexpression of PGRMC1 resulted
in increased cholesterol- and estradiol levels, indicating a contribution
of PGRMC1 to cholesterol homeostasis. Interestingly, PGRMC1 overex-
pressing cells established a higher sensitivity to statin treatment, indicat-
ing an increased dependence on cholesterol biosynthesis pathway in these
cells. Finally, a positive correlation between PGRMC1 and ERα expression
levels and -activation was identied, suggesting the activation of ERα sig-
naling by cholesterol metabolites.
Conclusions: PGRMC1 is potentially involved in cholesterol homeosta-
sis by modulation of enzymes of the respective biosynthesis pathway re-
sulting in elevated levels of cholesterol and its metabolites. Subsequent
activation of oncogenic signaling cascades could contribute to breast
cancer progression. erefore PGRMC1 represents a potential target for
anti-cancer therapy.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts6
Inhalt
2018
Index
2018
859
Serum- Cytokine Prole after Extended Liver Resection
Sandra Brückner 1; Laura Henneke 1; Michael Bartels 2;
Philipp Felgendre 3, 4; Uta Dahmen 4; Utz Settmacher 4;
Bruno Christ 1; Hans-Michael Tautenhahn 3, 4
1Clinics of Visceral, Transplantation, Thoracic and Vascular Surgery, University
Hospital Leipzig, Leipzig, Deutschland
2Clinics of General and Visceral Surgery, HELIOS Park-Klinikum Leipzig, Leipzig,
Deutschland
3Research Programme “Else Kröner-Forschungskolleg AntiAge”, University
Hospital Jena, Jena, Deutschland
4Clinics of General, Visceral and Vascular Surgery, University Hospital Jena, Jena,
Deutschland
Purpose: An extended partial hepatectomy (ePHx) is oen the only cura-
tive option for patients suering from primary or secondary liver tumors.
e substantial loss of liver parenchyma may lead to organ dysfunction
respectively liver failure. e molecular ways, which are accompanied by
liver failure, are not known in detail yet. For this reason this study should
show the change of cytokine proles aer liver resection.
Methods: In this study 100 cytokines in the serum of patients, undergoing
an ePHx (>70%) in cause of liver tumor, were determine. e cytokines
were quantied 24h before and aer liver resection with the Proteome
ProlerTMHuman Cytokine Array Kit (R&D systems).
Results: 14 out of 100 dened cytokines shows a signicantly higher level
24h aer liver resection compared to preoperative status. MIF (Macro-
phage migration inhibitory factor) and ST2 (Interleukin 1 receptor-like
1; Receptor for interleukin-33) shows more than doubling in the level of
intensity. Also Lipocalin-2, MMP9 (Matrix metallopeptidase 9), PDG-
FAA (Platelet-derived growth factor alpha polypeptide) and TFF3 (Trefoil
factor 3) were inuenced by the extended liver resection. e signicantly
inuenced cytokines were analyzed by the STRING database, resulting
in a calculation of the aected KEGG pathways. is calculation clearly
shows an eect of the liver resection on the TNF signaling pathway (path-
way ID: 04668) (p=0.00542) and the immune system process (pathway ID:
0002376) (p=9.52e-6).
Conclusions: Due to liver resection, a number of dierent immunological
processes will be inuenced. Based on this study the TNF signaling path-
way seems to be one of the main important processes in liver regenera-
tion in our mind. Identifying such pathways and detecting there inuence
in liver regeneration forms the foundation of developing new molecular
targets which will open up new therapeutic approaches supporting the
post-operative liver regeneration.
Disclosure Statement: nothing to declare
Breast Cancer
Vorträge
629
Impact of Chemotherapy-Induced Ovarian Failure (CIOF) on
Disease-Free Survival (DFS) and Overall Survival (OS) in Young
Women with Early Breast Cancer (EBC)
Jenny Furlanetto 1; Valentina Nekljudova 1; Andreas Schneeweiss 2;
Christian Thode 3; Carsten Denkert 4; Michael Untch 5; Martina Bassy 3;
Thomas Karn 6; Peter A. Fasching 7; Elmar Stickeler 8; Christian Schem 9;
Frederik Marmé 10; Eva-Maria Grischke 11; Marion van Mackelenbergh 12;
Dominika Strik 13; Sabine Schmatloch 14; Volkmar Müller 15; Sibylle Loibl 1
1GBG, Neu-Isenburg, Germany
2Nationales Centrum für Tumorerkrankungen, Heidelberg, Heidelberg, Germany
3Amedes MVZ wagnerstibbe für Laboratoriumsmedizin, medizinische
Mikrobiologie und Immunologie, Göttingen, Göttingen, Germany
4Institut für Pathologie Philipps-Universität Marburg, Marburg, Germany
5Helios Kliniken Berlin-Buch, Berlin, Germany
6Universitätsklinikum Frankfurt, Frankfurt, Germany
7University Hospital Erlangen, Erlangen, Germany
8Uniklinik RWTH Aachen, Aachen, Germany
9Mammazentrum Hamburg, Hamburg, Germany
10Universitätsfrauenklinik Mannheim, Mannheim, Germany
11Universitätsklinikum Tübingen, Tübingen, Germany
12Universitätsklinikum Schleswig-Holstein, Klinik für Gynäkologie und
Geburtshilfe, Schleswig-Holstein, Kiel, Germany
13Endokrinologikum Berlin, Berlin, Germany
14Elisabeth Krankenhaus Kassel, Kassel, Germany
15Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Purpose: Previous data has shown that chemotherapy (CT)-induced
amenorrhea was associated with a better DFS and OS in premenopausal
patients (pts) with EBC, regardless of the hormone receptor status.
Methods: 740 pts aged ≤45yrs treated with anthracycline/taxane (A/T)-
based CT for EBC from 4 German neo-/adjuvant trials were examined.
Centrally assessed estradiol (E2) and follicle-stimulating hormone (FSH)
in blood samples were collected at baseline and 4 wks aer the last
chemotherapy administration. CIOF was dened as E2 <52.2 ng/L and
FSH >12.4IU/L aer CT for pts with premenopausal hormone levels at
baseline (n=696). We present 4-year DFS and OS overall and in subgroups
by hormone receptor status and age.
Results: Median follow-up was 49.6 [48.8-50.3] months. Overall DFS: in
all pts without CIOF vs CIOF 65.2% vs 84.0%, p<0.001 (hazard ratio [HR]
2.06, 95%CI 1.36-3.12); in HR+ pts (n=395) 61.8% vs 87.5%, <0.001 (HR
2.69, 95%CI 1.57-4.60); in HR- pts (n=301) 71.6% vs 79.6%, p=0.266 (HR
1.47, 95%CI 0.74-2.89); in pts <30 yrs (n=60) 68.3% vs 92.6%, p=0.026
(HR 4.87, 95%CI 1.05-22.63); in pts 30-34 yrs (n=99) 59.9% vs 80.1%,
p=0.108 (HR 1.99, 95%CI 0.85-4.68); in pts 35-39 (n=200) yrs 63.5% vs
81.9%, p=0.116 (HR 1.85, 95%CI 0.85-4.04); in pts ≥40 yrs (n=337) 69.3%
vs 85.2%, p=0.565 (HR 1.41, 95%CI 0.44-4.51). OS in pts without CIOF
vs CIOF was 89.5% vs 92.7%, p=0.272 (HR 1.46, 95%CI 0.74-2.90); within
subgroups a trend towards a better OS was seen only in HR+ pts: 88.4% vs
95.9%, p=0.035 (HR 0.49, 95%CI 1.04-5.99).
Discussion: Our results support that pts with CIOF aer CT for EBC had
a better DFS compared to pts without CIOF, in particular if very young.
Moreover, we show that in HR+ BC, CIOF was associated with a signi-
cant improvement of DFS and OS.
Conclusions: Pts with CIOF aer A/T-based CT for EBC show a better
DFS, especially if <30 yrs or HR+. is DFS improvement translates in an
OS advantage in the latter group.
Reference:
1. Swain et al. NEJM 2010
Disclosure Statement: e study was supported by Walter Schulz Stiung.
AS reported grants from Celgene, Roche, AbbVie, Molecular Partner; personal
fees from Roche, AstraZeneca, Celgene, Pzer, Novartis, MSD, Tesaro, Lilly. VM
reported personal fees from Amgen, AstraZeneca, Diichi-Sankyo, Eisai, Pzer
Novartis, Roche, Celgene, Teva, Janssen-Cilag, Genomic Health, Hexal, Pierre
Fabre, MSD, Lilly, Tesaro, Nektar and grants from Novartis, Roche, Seattle Genet-
ics. PAF reported grants from Novartis, Biontech, Cepheid and personal fees from
Novartis, Roche, Pzer, Celgene, Daiichi-Sankyo, Teva, Astra Zeneca, Merck Sharp
& Dohme, Myelo erapeutics, Macrogenics, Eisai, Puma. MvM reported personal
fees from AstraZeneca, Novartis, Amgen.
e other co-authors had nothing to disclose.
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2018
Index
2018
Poster
114
Gibt es einen Zusammenhang zwischen Silikonimplantaten
und dem Anaplastisch-Großzelligem Lymphom?
Lukas Prantl 1; Britta Kühlmann 1; Uwe Von Fritschen 2
1Hochschulzentrum für Plastische Chirurgie, Universität Regensburg
2Plastische Chirurgie, Berlin
Purpose: Über 80% der Brustrekonstruktionen werden weltweit mit Im-
plantaten durchgeführt. Die Sicherheit dieser Medizinprodukte und vor
allem der Zusammenhang der Bildung eines sehr seltenen Tumors des
lymphatischen Systems, das Breast Implant Associated Anaplastic Large
Cell Lymphoma (BIA-ALCL) sowie die Entstehung eines unklaren Symp-
tomenkomplexes, dem Autoimmune/Inammatory Syndrome Induced
by Adjuvants (ASIA) werden diskutiert.
Die Inzidenz des BIA-ALCL wird in der Literatur sehr unterschiedlich
angegeben. Dies liegt an uneinheitlich verwendeten Klassikationssyste-
men, unstrukturierten Datensammlung, möglichen Doppelmeldungen
in die Register, unsicheren klinischen und pathologischen Angaben und
fehlenden Daten zur Anzahl implantierter Implantate als Denominator. In
Deutschland sind bisher zwölf Fälle gemeldet.
Methods: Anhand der im Tumorzentrum Regensburg erhobenen Daten
über 17 Jahren errechneten wir die Inzidenz des CD-30 positiven und
ALK negativen Lymphoms.
Results: Von 170.293 erfassten Tumoren bei einer Population von 2.1 Mil-
lionen waren zwölf Fälle CD30 positiv und ALK negativ. In keinem Fall
war der Tumor mit einem Burstimplantat assoziiert.
Conclusions: Anhand von Hochrechnungen können wir eine Inzidenz
des BIA-ALCL von 4 auf 1.000.000 Implantat Jahre angeben. Infolge han-
delt es sich bei dem BIA-ALCL um eine äußerst seltene Komplikation von
Silikonimplantaten.
Disclosure Statement: keine
119
Neratinib + Capecitabine Versus Lapatinib + Capecitabine
in Patients with HER2+ Metastatic Breast Cancer Previously
Treated with ≥ 2 HER2-Directed Regimens: The Multinational,
Randomized, Phase III Trial Nala
Cristina Saura 1; Thomas Decker 2; Urs Breitenstein 3; Andreas Müller 4;
Marianne Just 5; Jens Huober 6; Christian Schem 7; Marina Wirtz 8;
Bernhard Heinrich 9; Daniel Egle 10; Alexandre Bodmer 11;
Maximilian Borner 12; Serban Dan Costa 13; Adam Brufsky 14;
Nala Investigators 15
1Vall d’Hebron University Hospital, Barcelona, Spanien
2Gemeinschaftspraxis fuer Haematologie und Onkologie GbR, Ravensburg,
Deutschland
3Onkotentrum Zurich 04, Zurich, Schweiz
4Breast Unit, Kantonsspital Winterthur, Winterthur, Schweiz
5Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Deutschland
6Universitaetsklinikum Ulm, Brustzentrum, Ulm, Deutschland
7Mammazentrum Hamburg, Hamburg, Deutschland
8SAH Eschweiler, Eschweiler, Deutschland
9Haematologisch-onkologische Praxis, Augsburg, Deutschland
10Medizinische Universitaet Innsbruck, Innsbruck, Österreich
11Hôpitaux Universitaires de Genève, Geneva, Schweiz
12Brustzentrum Bern, Bern, Schweiz
13Otto-von-Guericke University Magdeburg, Magdeburg, Deutschland
14Magee-Womens Hospital of UPMC, Pittsburgh, PA, United States
Purpose: NALA (NCT01808573) is a multinational, randomized, open-la-
bel, phase III trial of neratinib (an irreversible pan-HER tyrosine kinase in-
hibitor [TKI]) + capecitabine (N+C) vs lapatinib (a reversible dual TKI) +
C (L+C) in patients with stage IV HER2+ metastatic breast cancer (MBC)
who had received ≥ 2 prior HER2-directed regimens for MBC.
Methods: Patients were randomized 1:1 to N (240 mg qd po) + C (750
mg/m2 bid po) or L (1250 mg qd po) + C (1000 mg/m2 bid po). Patients
on N had mandatory diarrhea prophylaxis. Co-primary endpoints were
centrally assessed progression-free survival (PFS) and overall survival
(OS). Secondary endpoints were objective response rate (ORR); duration
of response (DoR); clinical benet rate (CBR); time to intervention for
symptomatic metastatic central nervous system (CNS) disease; safety.
Results: 621 patients were randomized (307 to N+C; 314 to L+C). PFS
was improved with N+C vs L+C (HR = 0.76; 95% CI 0.63–0.93; p = 0.006);
6-month PFS rates were 47.2% vs 37.8% for N+C vs L+C, respectively. OS
rates at 12 months were 72.5% vs 66.7% (HR = 0.88; 95% CI 0.72–1.07;
p = 0.2086). ORR in patients with measurable disease was 32.8% with
N+C vs 26.7% with L+C (p = 0.1201) with longer DoR for N+C (HR =
0.50; 95% CI 0.33–0.74; p = 0.0004). CBR for N+C was 44.5% vs 35.6% for
L+C (p = 0.0328). Time to intervention for symptomatic CNS disease was
delayed with N+C vs L+C (overall cumulative incidence 22.8% vs 29.2%;
p = 0.043). Treatment-emergent adverse events (TEAEs) were similar be-
tween arms. G3 diarrhea was more frequent with N+C (24.4% vs 12.5%
for L+C) but with similar median duration (4 d). TEAE-related discontin-
uation rates were lower for N (10.9%) than for L (14.5%).
Conclusions: N+C signicantly improved PFS with a trend towards
improved OS vs L+C. N+C resulted in a reduced incidence of interventions
for CNS progression compared to L+C. No new safety signals were
observed.
e study was published at the ASCO Annual Meeting 2019.
142
Germline Mutation Status and Therapy Response in
High-Risk Early-Stage Breast Cancer: a Secondary Analysis
of the Geparocto Randomized Clinical Trial (NCT02125344)
Esther Pohl-Rescigno 1; Jan Hauke 1; Kerstin Rhiem 1; Volker Möbus 2;
Jenny Furlanetto 3; Carsten Denkert 4; Peter A. Fasching 5; Claus Hanusch 6;
Hans Tesch 7; Nana Weber-Lassalle 1; Volkmar Müller 8; Michael Untch 9;
Kristina Lübbe 10; Bianca Lederer 3; Christian Jackisch 11;
Valentina Nekljudova 3; Rita K. Schmutzler 1; Sibylle Loibl 3;
Andreas Schneeweiss 12; Eric Hahnen 1
1Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology
(CIO), University of Cologne, Faculty of Medicine and University Hospital
Cologne, Cologne, Deutschland
2Department of Gynecology and Obstetrics, Klinikum Frankfurt Höchst,
Academic Hospital of the Goethe University Frankfurt, Frankfurt, Deutschland
3German Breast Group (GBG), Neu-Isenburg, Deutschland
4Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum
Marburg, Marburg, Deutschland
5University Hospital Erlangen, Erlangen, Deutschland
6Rotkreuzklinikum, Frauenklinik, Munich, Deutschland
7Hämatologisch-Onkologische Gemeinschaftspraxis, Frankfurt, Deutschland
8Department of Gynecology, Hamburg-Eppendorf University Medical Center,
Hamburg, Deutschland
9Department of Gynecology and Obstetrics, Helios Klinikum Berlin-Buch, Berlin,
Deutschland
10Diakovere Henriettenstift, Breast Center, Hannover, Deutschland
11Sana Klinikum Oenbach GmbH, Oenbach, Deutschland
12National Center for Tumor Diseases, University of Heidelberg, Heidelberg,
Deutschland
Purpose: GeparOcto compared the ecacy of two neoadjuvant treatment
regimen in high-risk early breast cancer (BC): Sequential intense dose-
dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly
paclitaxel plus non-pegylated liposomal doxorubicin (PM), plus carbo-
platin (PMCb) in triple-negative BC (TNBC). ere was no dierence
in pathological complete response (pCR) rates (Schneeweiss et al. Eur J
Cancer. 2019;106:181-192).
Methods: Germline mutation analysis of BRCA1/2 and 16 further BC
predisposition genes using blood-derived DNA from 914 female patients
(pts) enrolled (393 pts with TNBC, 156 pts with HER2-/HR+ BC; and 365
pts with HER2+ BC). pCR rates (ypT0/is ypN0 denition) were stratied
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2018
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2018
according to the germline (g) mutation status overall, by treatment arm,
and tumor subtype.
Results: 96 of the 914 pts (10.5%) carried gBRCA1/2 mutations and
achieved higher pCR rates than pts without gBRCA1/2 mutations (60.4%
vs 46.7%, OR:1.74, P=.012). e gBRCA1/2 mutation prevalence was 17.6%
in TNBC, 14.1% in HER2-/HR+ BC, and only 1.4% in HER2+ BC. Irre-
spective of the treatment arm, pts with TNBC and gBRCA1/2 mutations
showed higher pCR rates compared with TNBC pts without gBRCA1/2
mutations (69.6% vs 46.0%, OR:2.69, P=.001). A positive gBRCA1/2 mu-
tation status predicts therapy response in both, the PMCb arm (74.3% vs
47.0%, OR:3.26, P=.005) and the iddEPC arm (64.7% vs 45.0%, OR:2.24,
P=.040); dierences between treatment arms did not reach levels of signif-
icance (P=.389). In the subgroup of pts with HER2-/HR+ BC, a positive
gBRCA1/2 mutation status predicts signicantly higher pCR rates (31.8%
vs 11.9%, OR:3.44, P=.020).
Conclusions: Eective chemotherapy for gBRCA1/2-mutated TNBC
is commonly suggested platinum-based. With a pCR rate of 64.7%, we
demonstrate that iddEPC appears to be similar eective in these pts. Of
interest is the signicantly higher pCR rate in HER2-/HR+ gBRCA1/2 car-
riers compared to non-carriers. e question arises whether all pts with
high-risk luminal BC should be oered gBRCA1/2 testing prior to treat-
ment start.
150
Factors Inuencing the Time to Surgery after Neoadjuvant
Chemotherapy in Breast Cancer Patients
Carolin Müller 1; Stephanie Juhasz-Böss 2; Gilda Schmidt 2;
Peter Jungmann 2; Erich-Franz Solomayer 2; Georg-Peter Breitbach 2;
Ingolf Juhasz-Böss 2
1Universitätsklinikum des Saarlandes, Gynäkologie, Geburtshilfe und
Reproduktionsmedizin, Homburg, Deutschland
2Universitätsklinikum des Saarlandes
Purpose: It is suspected, that delayed surgery aer neoadjuvant chemo-
therapy leads to a worse outcome in breast cancer patients. We therefore
determined time interval between the end of neoadjuvant chemotherapy
(NACT) and surgery, as well as possible inuencing factors.
Methods: All patients receiving NACT due to newly diagnosed breast
cancer from 2015 to 2017 at Department of Gynecology, Saarland Uni-
versity Medical School, were included. e time interval between end of
NACT and surgery was dened as primary endpoint. Possible delaying
factors were investigated: Age, study participation, outpatient and inpa-
tient presentations, implants/expander, MRI preoperatively, discontinua-
tion of chemotherapy, genetic mutations.
Results: Data of 139 patients was analyzed. e average age was 53 years
(+/- 13). e time interval between end of NACT and surgery was 28 days
(±9). Clinical presentations on outpatient and inpatient basis showed a
statistically signicant prolonging eect on the time between NACT and
surgery (p=0.002; p<0.001). Also, discontinuation of NACT led to a pro-
longed time to surgery (p=0.005). In contrast, a proven genetic mutation
shortened the time to surgery (p<0.001).
Conclusions: Every outpatient presentation prolonged the time to sur-
gery by an average of two days, inpatient presentations prolonged the time
to surgery by an average of seven days. Discontinuation of NACT delayed
surgery by an average of six days. Patients with proven genetic mutation
had surgery seven days earlier. Patients age, participation in clinical stud-
ies, oncoplastic surgery and preoperative MRI scans did not delay therapy
onset.
152
The Potential of Claims Data for Long-Term Follow-Up
of Breast Cancer Patients in Germany
Miriam Heinig 1; Ulrike Haug 1, 2
1Leibniz-Institut für Präventionsforschung und Epidemiologie – BIPS GmbH,
Bremen, Deutschland
2Universität Bremen, Fakultät Human- und Gesundheitswissenschaften,
Bremen, Deutschland
Purpose: Population-based data on long-term treatment patterns and
clinical outcomes in cancer patients are important but hardly available
from German cancer registries. Exemplied by breast cancer (BC) pa-
tients, we aimed to explore the potential of German claims data for pro-
viding long-term follow-up information on cancer patients.
Methods: We used the German Pharmacoepidemiological Research Da-
tabase (GePaRD) containing claims data from four statutory health in-
surances with information on ~25 million persons. Based on previously
developed algorithms using ICD-10 codes, we identied patients newly
diagnosed with BC in 2008 and classied them into three groups: no af-
fected lymph nodes/metastasis (noNM), aected lymph nodes only (on-
lyN) or distant metastasis (M) at diagnosis. e cohort was followed up
until end of 2016 or death. We characterized the groups regarding initial
and subsequent therapies (surgery, medical therapy and radiotherapy),
metastases and deaths occurring during follow-up.
Results: Aer exclusion of patients switching health insurance during
follow-up (9% of the initial cohort) we included 11,717 BC patients diag-
nosed in 2008 (noNM: 82%, onlyN: 12%, M: 7%) with a mean age of 63
years (median follow-up: 8.4 years). During the observation period, 11%
of the cohort received no breast surgery (group M: 21%), 28% received
more than one surgery (second surgery in rst year: 81%; later: 19%) and
29% had a mastectomy (in rst year: 91%, only later: 9%). Of the total
cohort, 8% received neoadjuvant therapy, 7% ever received monoclonal
antibodies, 52% never received chemotherapy (group noNM: 92%) and
28% never received radiotherapy. Overall, 25% of the cohort died (group
M: 22%).
Conclusions: Claims data provide valuable information on the long-term
course and treatment of cancer patients, avoiding substantial loss-to-fol-
low-up and incomplete reporting of therapies. Combining claims data
with cancer registry data containing detailed tumor information may cre-
ate synergies that should be explored.
Disclosure Statement: None.
153
HER4 Expression in Estrogen Receptor-Positive Breast
Cancer is Associated with Decreased Sensitivity to Tamoxifen
Treatment and Reduced Overall Survival of Postmenopausal
Women
Gero Brockho 1; Dominik Chittka 2; Stefan Buchholz 3;
Simone Diermeier-Daucher 3; Monika Klinkhammer-Schalke 4;
Florian Zeman 5; Anja-Kathrin Wege 1; Olaf Ortmann 1
1Klinik für Frauenheilkunde und Geburtshilfe, Universität Regensburg,
Deutschland
2Klinik für Innere Medizin II, Universität Regensburg, Deutschland
3Klinik für Frauenheilkunde und Geburtshilfe, Universität Regensburg,
Regensburg, Deutschland
4Institut für Qualitätssicherung Versorgungsforschung, Tumorzentrum,
Universität Regensburg, Deutschland
5Zentrum für Klinische Studien, Universität Regensburg, Deutschland
Purpose: e sensitivity of estrogen receptor positive breast cancers to
tamoxifen treatment varies considerably and the molecular mechanisms
aecting the response rates are manifold. e human epidermal growth
factor receptor related receptor HER2 is known to trigger intracellular sig-
naling cascades that modulate the activity of coregulators of the estrogen
receptor which in turn reduces the cell sensitivity to tamoxifen treatment.
However, the impact of HER2 related receptor tyrosine kinases HER1,
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Inhalt
2018
Index
2018
HER3, and in particular HER4 on an endocrine treatment eciency is
largely unknown.
Methods: Here we retrospectively evaluated the importance of HER4
expression on the outcome of tamoxifen and aromatase inhibitor treated
estrogen receptor positive breast cancer patients (n = 258) – either pre- or
postmenopausal. In addition, we experimentally analyzed the eciency of
tamoxifen treatment as a function of HER4 coexpression in-vitro.
Results: We found a signicantly improved survival of tamoxifen treated
postmenopausal breast cancer patients in the absence of HER4 compared
to those with pronounced HER4 expression. In accordance with this nd-
ing the sensitivity to tamoxifen treatment of estrogen and HER4 recep-
tor positive ZR-75-1 breast cancer cells can be signicantly enhanced by
HER4 knockdown.
Conclusions: We suggest an HER4 / estrogen receptor interaction that
impedes tamoxifen binding to the estrogen receptor and reduces treat-
ment eciency. Whether the sensitivity to tamoxifen treatment can be
enhanced by an anti-HER4 targeting needs to be prospectively evaluated.
Reference:
1. Brockho G. Target HER four in breast cancer? Oncotarget. 2019 May
7;10(34):3147-3150.
[…] Brockho G. HER4 expression in estrogen receptor-positive breast cancer
is associated with decreased sensitivity to tamoxifen treatment and reduced
overall survival of postmenopausal women. Breast Cancer Res. 2018 Nov
20;20(1):139.
Disclosure Statement: e authors declare no conicts of interest.
160
Capivasertib (AZD5363) Plus Fulvestrant Versus Placebo Plus
Fulvestrant After Relapse or Progression on an Aromatase
Inhibitor in Metastatic ER-Positive Breast Cancer (Faktion): a
Randomized, Double-Blind, Placebo-Controlled, Phase II Trial
Joke Tio 1; Artur Kokornaczyk 2; Björn Tschalener 2; Rober Hugh Jones 3
1Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Münster,
Münster, Deutschland
2AstraZeneca GmbH, Wedel, Deutschland
3Velindre Cancer Centre, Velindre Cancer Centre, Cardi, United Kingdom
Purpose: e PI3K/AKT signaling pathway is frequently activated in pa-
tients (pts) with estrogen receptor (ER) positive breast cancer (ER+BC)
and has been implicated in endocrine therapy resistance. Capivasert-
ib (Capi) is a highly-selective, oral, small molecule AKT inhibitor. e
FAKTION trial investigated the addition of Capi to fulvestrant (Ful) for
postmenopausal women with ER+ and HER2- BC aer relapse or disease
progression on an aromatase inhibitor (AI).
Methods: FAKTION is an investigator-led, double-blind, placebo-con-
trolled, randomised phase II trial. Patients were recruited from 21 UK
sites and randomly assigned (1:1) to Ful 500mg (day 1 and 15 of cycle 1
and day 1 only of subsequent 28 day cycles) with either Capi 400mg bd or
placebo (4 days on/3 days o starting C1D15) until disease progression,
unacceptable toxicity or withdrawal of consent. Allocation was balanced
by minimisation according to PIK3CA mutation and PTEN expression
status, measurable/non-measurable disease, and primary/secondary en-
docrine resistance. e primary endpoint was PFS. e trial had 90%
power to detect a hazard ratio of 0.65 at the one-sided 20% signicance
level. Secondary endpoints included OS, ORR and clinical benet rates,
safety and the eect of PI3K/AKT pathway activation on PFS.
Results: Between Mar 2015 and Mar 2018, 140 pts were randomised to
Ful + Capi (n = 69) or Ful + placebo (n = 71). In the ITT analysis, aer 112
events, mPFS was 10.3 months (m) for Capi compared to 4.8m for placebo
(HR 0.57; 95% CI: 0.39 to 0.84; one-sided p = 0.0017; two-sided 0.0035).
Fiy-two deaths were reported. Median OS was 26.0m for Capi compared
to 20.0m for placebo, with a survival dierence starting to emerge aer
12m (HR = 0.59; 95% CI: 0.34 to 1.05; two-sided p = 0.071).
Conclusions: e trial met its primary endpoint. Addition of Capi to Ful
for patients with endocrine resistant advanced breast cancer resulted in
signicantly longer PFS and an improvement in OS. Results warrant fur-
ther investigation of Capi for the treatment of ER positive breast cancer.
162
Identication of a Novel Gene Disrupting Germline Mutation
Derived from L1PA7 Transposition Into The BRCA2 Coding
Sequence: Further Improvement of the Trurisk® Gene Panel
Analysis
Esther Pohl-Rescigno; Corinna Ernst; Jan Hauke; Gizem Sahin;
Lisa Richters; Julia Driesen; Mohamad Kayali;
Barbara Wappenschmidt; Rita K. Schmutzler; Eric Hahnen
Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology
(CIO), University of Cologne, Faculty of Medicine and University Hospital
Cologne, Cologne, Deutschland
Purpose: Although the sensitivity of molecular geneticdiagnostics has
been improved by next generation sequencing (NGS) applications, no
causal mutations can be identied in many high-risk breast and ovari-
an cancer(BC/OC) families. One possible reason is the existence of yet
unknown genetic risk factors; another explanation is the limitation of
NGS analyses e.g. the identication of large insertions (Qian et al. Cancer
Genet. 2017). By re-analyzing NGS data, we focused on identifying gene
disruptions by large insertions of mobile genetic elements.
Methods: An in-house approach was employed to scan BWA (Bur-
rows-Wheeler Aligner)-MEM (maximal exact matches) algorithm-pro-
duced read mappings of 4,218 BC/OC index patients for accumulations
of break points in split-read alignments (Li 2013. arXiv:1303.3997). We
performed long-range polymerase chain reaction (PCR) by using primers
anking the predicted insertion breakpoint c.3258_3259 in BRCA2, sub-
sequent Sanger sequencing of gel-extracted PCR products, and sequence
analysis of the insertion using RepeatMasker.
Results: We were able to identify a novel insertion c.3258_3259insL1 in
BRCA2 which is predicted to cause a frameshi and premature protein
truncation p.(Ile1086Metfs*54) resulting in the loss of 2,280 amino ac-
ids. erefore, loss of BRCA2 function is very likely and the variant can
be classied as pathogenic (IARC class 5). e insertion derives from the
transposition of ~400 bp of the 3´-end of human retrotransposon LINE-1
(L1Hs), also known as L1PA7, into the BRCA2 coding sequence.
Conclusions: Re-analyzing NGS data from 4,218 BC/OC index cases, we
identied the novel BRCA2-disrupting insertion c.3258_3259insL1 in a
female patient with bilateral BC (age at rst diagnosis 30 and 36 years). Al-
though only identied once, this study underlines the need for continuous
improvement of bioinformatic NGS data analysis. Detection of unusual
pathogenic variants further improves the sensitivity of routine diagnostics
in order to provide the best possible counselling and risk calculation to
those seeking advice.
167
Clinical Signicance of PIK3CA and ESR1 Mutations in CTDNA
and FFPE Samples from The Monarch2 Study of Abemaciclib
Plus Fulvestrant
Eva Maria Grischke 1; Sara Tolaney 2; Masakazu Toi 3; Patrick Neven 4;
Joo Hyuk Sohn 5; Antonio Llombart-Cussac 6; Hatem Soliman 7;
Lacey Litcheld 8; Sameera Wijayawardana 8; Tammy D Forrester 8;
Valerie Jansen 8; George W Sledge 9
1Tübingen, Universität Tünbingen, Tübingen, Deutschland
2Boston, Harvard University, Boston, United States
3Kyōto, Kyoto University, Kyōto, Japan
4Löwen, Universitaire Ziekenhuizen Leuven, Löwen, Belgien
5Seoul, Yonsei Cancer Center, Seoul, Südkorea
6Valencia, Hospital Arnau Vilanova, Valencia, Spanien
7Tampa, Mott Cancer Center, Tampa, United States
8Indianapolis, Eli Lilly and Company, Indianapolis, United States
9Stanford, Stanford University, Stanford, United States
Purpose: We assessed clinical signicance of PIK3CA and ESR1 muta-
tions from patients treated with abemaciclib (A)+fulvestrant (F) and pla-
cebo (P)+F.
Methods: Baseline plasma samples (n=334) and FFPE tumor samples
(n=434) from 669 MONARCH2 patients were analyzed. Extracted DNA
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was analyzed by droplet digital PCR for 4 hotspot mutations of PIK3CA
(E542K; E545K; H1047L; H1047R) and ESR1 (D538G; Y537C; Y537N;
Y537S). Samples failing DNA QC or with mutation status undetermined
were excluded from analysis.
Results: PIK3CA mutations were detected in 40.3% of plasma and 39.9%
of FFPE samples. H1047R was the most frequent mutation. Concordance
of PIK3CA mutations in ctDNA and FFPE samples was 62.8%. ESR1
mutations were detected in 64.4% of plasma and 4.4% of FFPE samples.
D538G was the most frequent mutation. Concordance of ESR1 mutations
in ctDNA and FFPE samples was 37.1%; this is explained in part by the
biopsy site (primary vs metastatic). Co-mutations in PIK3CA and ESR1
were observed in 36.1% plasma and 1.5% FFPE samples. In PIK3CA wild-
type (WT) median PFS was 20 mo for A+F and 12.7 mo for P+F (HR:
0.68; 95%CI: 0.42, 1.09); PIK3CA mutant (M): median PFS=15 mo for
A+F and 5.7 mo for P+F (HR: 0.46; 95%CI: 0.27, 0.78); ESR1 WT: median
PFS=16.3 mo for A+F and 11.6 mo for P+F (HR: 0.69; 95%CI: 0.41, 1.18);
ESR1 M: median PFS=21.9 mo for A+F and 10.3 mo for P+F (HR: 0.49;
95%CI: 0.33, 0.73).
Conclusions: PIK3CA and ESR1 mutations in ctDNA correlated with
response to A. Addition of A to F improved PFS regardless of PIK3CA/
ESR1 status; however, magnitude of benet was numerically greater when
PIK3CA/ESR1 mutations were present.
168
A Phase 2 Study of Abemaciclib in Patients (PTS) with Brain
Metastases (BM) Secondary to HR+, HER2 Metastatic Breast
Cancer (MBC)
Carey Anders 1; Emily Le Rhun 3; Thomas Bachelot 4; Denise Yardley 5;
Ahmad Awada 6; Pierre Franco Conte 7; Peter Cabos 8; Melissa Bear 9;
Sarah Tolaney 10
1Durham, Duke Cancer Institute, Durham, United States
2München, Technische Universität München, München, Deutschland
3Lille, University Hospital, Lille, Frankreich
4Lyon, Centre Leon Berard, Lyon, Frankreich
5Nashville, Sarah Cannon Research Institute, Nashville, United States
6Brüssel, Institut Jules Bordet, Brüssel, Belgien
7Padua, University of Padova, Padua, Italien
8Denver, University of Denver, Denver, United States
9Indianapolis, Elli Lilly, Indianapolis, United States
10Boston, Dana-Farber Cancer Institute, Boston, United States
Purpose: Clinical data demonstrate that abemaciclib penetrates blood-
brain with comparable concentrations in tissues and plasma.
Methods: JPBO is a Simon 2-stage trial evaluating abemaciclib in 6 pt
cohorts with BM secondary to HR+ MBC, non-small cell lung cancer,
or melanoma. We report on HR+, HER2- MBC pts. Eligible pts had ≥1
new or not previously irradiated measurable BM ≥10mm or a progressive
previously irradiated BM. Endocrine therapy (ET) was permitted to be
continued provided that extracranial disease was stable ≥3 months and
BM progression occurred on the ET. Abemaciclib was orally adminis-
tered 200mg BID. Primary endpoint was objective intracranial response
rate (OIRR; [complete response (CR)+partial response (PR)]) based on
Neuro-Oncology BM response assessment criteria. Secondary endpoints
were intracranial clinical benet rate, progression-free survival (PFS), and
safety.
Results: 58 pts were enrolled; 52 were evaluable. Pts had median of 4pri-
or systemic therapies, 75% had prior chemotherapy (0-6, median 2), 71%
had prior ET (0-4, median 1) in the metastatic setting. 50% pts had pri-
or whole-brain radiotherapy (RT), 39% stereotactic radiosurgery and 8%
surgical BM resection. Median time from RT to study enrollment was 9.4
months. Out of 52 evaluable pts, 3 had a conrmed intracranial response
(6% OIRR); 38% had a decrease in the sum of intracranial target lesions.
Intracranial clinical benet rate (CR+PR+stable disease persisting for ≥6
months) was 25%. Median PFS was 4.4 months (95%CI 2.6-5.5). Safety
and tolerability were similar to previous reports for abemaciclib.
Conclusions: Abemaciclib demonstrated intracranial clinical benet in
the study pts. Further evaluations are ongoing to identify MBC pts with
BM who might benet most from abemaciclib.
182
Breast Units – a Comparison of the Landscape in Germany
and the United Kingdom
Sandra Breitenbücher 1; Rüdiger Meierjürgen 2; Wilfried Boroch 2
1Stabsstelle Qualitätsmanagement und klinisches Risikomanagement,
Universitätsklinikum Essen, Essen, Deutschland
2FOM Hochschule für Oekonomie & Management, Essen, Deutschland
Purpose: Survival rates of Breast Cancer patients still dier in European
countries. Studies like the EUROCARE-5 study show a lower 5-year-sur-
vival-rate in Eastern Europe and the United Kingdom (UK)/Ireland com-
pared to the European average and Germany. 1 Here we select key per-
formance indicators (KPIs) with presumable impact on survival of Breast
Cancer patients and compare certication/inspection systems in Germa-
ny and the UK. We focus on the systems of OnkoZert (Germany), the
Care Quality Commission (CQC, England) and the European Society of
Mastology (EUSOMA). Utilization of certication systems like OnkoZert
and EUSOMA is voluntary, whereas the CQC keeps the care providers
under obligatory surveillance.
Methods: KPI selection resulted from literature analysis and an expert
survey. Experts were dened as people involved in Breast Cancer patient
care (i.e. physicians, nurses and people working in quality management or
certifying bodies). 78 experts were asked to ll in a short questionnaire.
e rate of return was 68%.
Results: Selected KPIs assumed to have a positive impact on the survival
rate of Breast Cancer patients were for example an early stage diagnosis, a
short interval between diagnosis and start of therapy, early access to new
therapies and a multidisciplinary collaboration of the treatment team.
Many of the selected KPIs were integrated into the requirements of the
analyzed certication/inspection systems. However, the level of detail and
frequency of inspection diered markedly.
Conclusions: Harmonization of certication systems on a European level
seems to be reasonable. More than 90% of the responding experts are con-
vinced that certication of Breast Units has a positive impact on care and
survival of Breast Cancer patients.
Reference:
1. Vgl. Sant, M. et al., Survival of women with cancers of breast and genital
organs in Europe 1999-2007[…] in: European Journal of Cancer, 2015, S. 2191
.; Allemani, C. et al.,Global surveillance of trends in cancer survival 2000-14
(CONCORD-3)[… ] in: e Lancet, 2018, S. 1023 .
Disclosure Statement: No disclosures.
184
Routine Care Reality of Patients with Metastatic Anti-Human
Epidermal Growth Factor Receptor 2 (HER2) Positive Breast
Cancer Who Received Treatment in Oncology Group Practices
in Germany Between 2012 and 2017
Rudolf Weide 1; Bernhard Rendenbach 2; Hans-Peter Laubenstein 2;
Ute Braun 3; Karl Hünermund 3; Oswald Burkhard 4; Peter Ehscheidt 5;
Stefan Feiten 6; Geothy Chakupurakal 1; Vera Friesenhahn 6;
Kristina Kleboth 6; Hubert Köppler 1; Julia Lutschkin 6; Jörg Thomalla 1;
Christoph van Roye 1; Jochen Heymanns 1
1Praxis für Hämatologie und Onkologie, Koblenz, Deutschland
2Praxis für Hämatologie, Onkologie und Nephrologie, Trier, Deutschland
3Gemeinschaftspraxis für Hämatologie und Onkologie, Ludwigshafen,
Deutschland
4Internistische Gemeinschaftspraxis Hämatologie, Onkologie, Palliativmedizin,
Worms, Deutschland
5Onkologische Praxis Dr. Ehscheidt, Neuwied, Deutschland
6Institut für Versorgungsforschung in der Onkologie, Koblenz, Deutschland
Purpose: Many treatment options have become available since the discov-
ery of an overexpression of HER2 in approximately 15–25% of all breast
cancer patients. Real world data concerning treatment sequences and out-
come from unselected patients who receive routine care are not known.
Methods: Retrospective analysis of all patients with metastatic HER2
positive breast cancer who were treated between 01/2012 and 12/2017 in
ve community-based oncology group practices in Germany. Data were
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extracted from patient les into a database and analyzed statistically using
SPSS.
Results: 146 female patients with a median age of 59.5 years (24–91) were
analyzed. 35% were in stage IV at diagnosis, 75% were hormone receptor
positive. Localizations of metastases were distributed as follows: 55% vis-
ceral, 17% bone, 5% CNS, 8% lymph nodes and 9% others. 1st line Anti
HER2 therapy consisted of trastuzumab+pertuzumab in 54%, trastuzum-
ab in 36%, lapatinib in 5% and trastuzumab emtansine in 4%. 2nd line
treatment was trastuzumab+pertuzumab in 63%, trastuzumab in 23%,
trastuzumab emtansine in 7%, lapatinib in 4% and trastuzumab+lapati-
nib in 2%. 3rd line therapy consisted of trastuzumab emtansine in 43%,
trastuzumab in 28%, trastuzumab+pertuzumab in 23% and lapatinib in
8%. Median overall survival (OS) was 54 months (1.1-69.4). OS was sig-
nicantly correlated with hormone receptor status. Patients with triple
positive tumors had a median OS of 56 months (3.8-69.4) compared to
33 months (1.1-62.1) in HER2 only positive patients (p=.004). OS depen-
dent strongly but not statistically signicant on the number of metastasis
localizations. Median OS of patients with 1 localization was 54.0 months
(1.1-69.4) compared to 40.8 months (2.1-56.4+) in patients with two or
more localizations.
Conclusions: OS improvements of patients with metastatic HER2 pos-
itive breast cancer are strongly restricted to hormone receptor positive
tumors most likely due to improved targeted therapies directed against
HER2 and the estrogen receptor.
Disclosure Statement: All authors report no conicts of interest
215
First Results of the Detect IVA Study –Everolimus Treatment
in Patients with HER2-Negative, Hormone-Receptor Positive
Metastatic Breast (MBC) Cancer and Circulating Tumor Cells
(CTC)
Thomas W. P. Friedl 1; Sabrina Krause 1; Peter Andreas Fasching 2;
Andreas Schneeweiss 3; Volkmar Müller 4; Sabine Riethdorf 5;
Florin-Andrei Taran 6; Fabienne Schochter 1; Arkadius Polasik 1;
Marie Tzschaschel 1; Amelie De Gregorio 1; Franziska Meier-Stiegen 7;
Jens Huober 1; Wolfgang Janni 1; Tanja Fehm 7
1Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm,
Deutschland
2Department of Gynecology and Obstetrics, University Hospital Erlangen,
Erlangen, Deutschland
3Department of Gynecology and Obstetrics, University of Heidelberg,
Heidelberg, Deutschland
4Department of Gynecology and Obstetrics, University Hospital Hamburg-
Eppendorf, Hamburg, Deutschland
5Department of Tumor Biology, University Hospital Hamburg-Eppendorf,
Hamburg, Deutschland
6Department of Gynecology and Obstetrics, University Hospital Tübingen,
Tübingen, Deutschland
7Department of Gynecology and Obstetrics, University Hospital Düsseldorf,
Düsseldorf, Deutschland
Purpose: e DETECT-IVa trial is a single-arm, open-label phase II study
for postmenopausal patients with HER2-negative, hormone-receptor pos-
itive MBC and HER2-negative CTCs. One of the main aims is to evaluate
the suitability of CTCs to provide both prognostic and predictive infor-
mation.
Methods: e DETECT IVa trial started in February 2014 and compris-
es two subsequent patient cohorts – the rst cohort received endocrine
therapy combined with the mTOR inhibitor everolimus, while the second
cohort of this ongoing trial receives endocrine therapy combined with the
CDK 4/6 inhibitor ribociclib. We performed an unplanned interim analy-
sis (data cuto July 2019) to obtain preliminary, rst results with regard to
patient characteristics, presence of CTCs 3 to 12 weeks aer study initia-
tion and overall survival (OS) for the rst (everolimus) cohort comprising
90 patients.
Results: Median age of the 90 patients of the everolimus cohort was 63
years (range 40 – 88 years). Median number of CTCs detected at baseline
was 5.5 (range 1 – 400 CTCs). At the time of data cuto, end of study treat-
ment was documented for 71 patients. 7 out of 8 patients that received
everolimus for the full study treatment period (12 months) had no CTCs
aer 3 to 12 weeks (no CTC data for one patient). 63 patients had to ter-
minate everolimus treatment prematurely because of death (6.3%), prog-
ress (58.7%), patients wish (11.1%), non-hematological toxicity (20.6%)
or treatment delays (3.2%). 23 (51.1%) out of 45 patients with premature
termination of everolimus treatment and available CTC data showed pres-
ence of CTCs aer 3 to 12 weeks. Median OS for 56 patients with data
available was 18.9 months (95% condence interval 11.8 – 26.0 months),
and presence of CTCs aer 3 to 12 weeks was signicantly associated with
poor OS (log rank test, p = 0.046).
Conclusions: Preliminary rst results of the DETECT-IVa trial indicate
that everolimus is still a valuable option for postmenopausal patients with
HER2-negative, hormone-receptor positive MBC. CTC detection pro-
vides prognostic information also in this clinical context.
232
A Real-World Evidence Study of CDK4/6 Inhibitor Treatment
Patterns and Outcomes in Metastatic Breast Cancer by
Gbrcamutation Status
Michael Untch1, Peter Andreas Fasching2, Kimmie Mclaurin3
1Helios Klinikum Berlin-Buch, Berlin, Deutschland
2Universitätsklinikum Erlangen, Frauenklinik, Erlangen, Deutschland
3AstraZeneca Pharmaceuticals, AstraZeneca Pharmaceuticals, Gaithersburg,
United States
Purpose: Limited data exist on the real-world treatment patterns and ef-
fectiveness of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in
the germlineBRCA(gBRCA) mutated breast cancer population.
Methods: Adults with human epidermal growth factor receptor 2 nega-
tive (HER2-), hormone receptor positive (HR+) metastatic breast cancer
(mBC) treated with a CDK4/6 inhibitor from 01Jan2013–31Jan2018 were
retrospectively selected from the Flatiron Health Oncology electronic
medical record database. Patients with known gBRCAstatus were clas-
sied as having gBRCA mutated (gBRCAm) or wild type (gBRCAwt)
disease. Time to rst subsequent therapy or death (TFST) and overall sur-
vival (OS) were calculated from start of the earliest line of therapy with
a CDK4/6 inhibitor. Kaplan-Meier (KM) medians were estimated, and
TFST and OS compared between gBRCAgroups with Cox models strat-
ied by line of therapy and adjusting for demographic and clinical char-
acteristics that modied hazard ratios (HRs) for gBRCAstatus by > 10%.
Results: Of 2968 HER2- HR+ patients with mBC receiving a CDK4/6 in-
hibitor, gBRCAstatus was known for 859 (28.9%). Patients with gBRCAm
and gBRCAwt received letrozole plus palbociclib (42.4 and 39.8%, respec-
tively), fulvestrant plus palbociclib (32.9 and 30.7%), or other CDK4/6
regimens (24.7 and 29.5%) across all lines. e gBRCAm group had a
non-signicant, shorter TFST than gBRCAwt (stratied HR 1.24; 95% CI
0.96–1.59). OS was signicantly shorter in gBRCAm than gBRCAwt pa-
tients (stratied HR 1.50; 95% CI 1.06–2.14).
Conclusions: e results of this real-world study suggest that treat-
ment outcomes with CDK4/6 inhibitors may be poorer in patients with
gBRCAm compared with gBRCAwt disease. ese ndings indicate a
higher unmet need among patients with gBRCAm, potentially requiring
alternative treatment options.
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254
Routine Care of Advanced Breast Cancer: The Prospective,
National Research Platform Opal for Patients with Advanced
Breast Cancer in Germany
Thomas Decker 1; Nadia Harbeck 2; Marc Thill 3; Mark-Oliver Zahn 4;
Arnd Nusch 5; Andreas Lorenz 6; Ulrike Söling 7; Marco Chiabudini 8;
Lisa Kruggel 8; Martina Jänicke 8; Norbert Marschner 9; Elmar Stickeler 10;
Achim Wöckel 11; Anja Welt 12
1Gemeinschaftspraxis für Hämatologie und Onkologie, Ravensburg,
Deutschland
2Brustzentrum, Klinik der Universität München (LMU), München, Deutschland
3Agaplesion Markus Krankenhaus, Frankfurt a.M., Deutschland
4Überörtliche Berufsausübungsgemeinschaft, Goslar, Deutschland
5Praxis für Hämatologie und internistische Onkologie, Ratingen, Deutschland
6Frauenarztpraxis Dr. Lorenz, Hildburghausen, Deutschland
7Hämato-Onkologisches Zentrum Kassel GmbH, Kassel, Deutschland
8iOMEDICO, Freiburg im Breisgau, Deutschland
9Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg i.Br.,
Deutschland
10Universitätsklinikum Aachen AöR für die Medizinische Fakultät, Aachen,
Deutschland
11Universitätsklinikum Würzburg, Würzburg, Deutschland
12Universitätsklinikum Essen (AöR), Essen, Deutschland
Purpose: e Tumor Registry Breast Cancer (TMK) has prospectively
documented treatment and outcome of patients (pts) with breast cancer
(BC) by oncologists in Germany since 2007. OPAL continues this success-
ful work focusing on changes in treatment reality of advanced BC (ABC),
patient-reported outcomes (PROs) and representation of all specialists
(medical and gynecologic oncologists) treating ABC in Germany.
Methods: OPAL like the TMK is a prospective, observational, open, mul-
ticentre clinical registry. In addition to the 4500 pts from the TMK, at least
2000 pts will be recruited in OPAL, stratied into 3 cohorts: 1000 pts with
hormone receptor positive, HER2-negative, 500 pts with HER2-positive
and 500 pts with triple-negative ABC. In total, up to 200 sites (compre-
hensive cancer centres, clinics and oce-based gynecologic and medical
oncologists) will be participating. All pts are recruited at start of their rst
palliative systemic treatment to avoid overestimation of outcome data.
OPAL collects detailed information on all (sequential) treatments, patient
and tumor characteristics, physician-reported factors inuencing treat-
ment decision, biomarker testing and additional treatments. Follow-Up
is until death or up to 5 years. Associated projects are a decentralized bio-
bank and the collection of PROs in clinical routine (every 3 months for
3.5 years).
Results: By August 2019, a total of 5319 pts had been recruited, 677 since
the start of OPAL in December 2017. 2348 pts with ABC recruited by 130
sites are now available for analyses of the combined TMK/OPAL database.
First results from the interim analysis 2019 will be presented.
Conclusions: OPAL will show how the choice of treatment changes over
time, which sequential treatments are applied and what the eectiveness
and PROs are in a “real world” setting. It will reveal the impact of new
treatments in pts in routine care and allow to identify areas for improve-
ment of care.
Disclosure Statement: None of the authors declare conicts of interests regarding
the topic of this abstract.
257
Skeletal-Related Events in Patients with Breast Cancer and
Bone Metastases: Frequency, Predictors and Mortality in a
Real-World Setting
Ingo Diel 1; Lennart Hickstein 2; Josephine Jacob 2; Eugen Dornstauder 3;
Michael Kellner 3; David Hohmann 4
1Mannheim, Praxisklinik am Rosengarten, Mannheim, Deutschland
2Berlin, InGef - Institut für angewandte Gesundheitsforschung Berlin GmbH,
Berlin, Deutschland
3München, Amgen GmbH, München, Deutschland
4München, Privater Beitrag: Früher Amgen GmbH, München, Deutschland
Purpose: Breast cancer is the most common cancer among women
in Germany with more than 70,000 new cases per year. In contrast the
mortality rate is much lower (20%). A large proportion of patients with
advanced disease are aected by bone metastases, or BM, (80%) and
skeletal-related events (SREs) resulting from BM. Moreover, observational
studies of patients with prostate cancer and BM have shown an association
between an increase of SREs and poorer survival. is study aims to
investigate this association in breast cancer patients with BM in a real-
world setting.
Methods: Data were obtained for analysis from the health claims InGef
database and limited to female breast cancer patients with newly diag-
nosed BM between 2012 and 2015. Event rates (ER) for distinct SREs were
calculated per 5 person-years (PY). In addition, using a time dependent
multivariate cox regression, we rst quantied the association between
SREs and all-cause death and second, through an exploratory analysis, we
evaluated the relation between use of bone-targeted agents (BTAs) and
SREs.
Results: e study population comprised of 2,522 female breast cancer
patients with a mean age of 65,8 years (SD +/- 13,0). ER per 5 PY var-
ied in frequency starting from radiation to the bone (ER=1.72), surgery
to the bone (ER=0.53) and pathologic fractures (ER=0.47) to spinal cord
compression (ER=0.07). Signicant associations (p<0,05) for a higher
risk of all-cause death were identied for the SREs pathologic fractures
(HR=2.41, 95% CI: 2.06-2.81) and radiation to the bone (HR=1.55, 95%
CI: 1.39-1.74). Finally, an exploratory analysis revealed that patients treat-
ed with BTAs experienced a 42% reduction in the risk of developing SREs
(HR=0.58, 95% CI: 0.47-0.71).
Conclusions: Our study shows that pathologic fractures and radiation
to the bone are common SREs in advanced breast cancer patients, both
leading to a higher risk of earlier death in this population. Treatment with
BTAs reduce the risk of developing SREs and therefore may lead to longer
survival in these patients.
Conicts of Interest:
is study was sponsored by Amgen GmbH which provided funding to WIG2
GmbH for the execution of the study and medical writing support. InGef –
Institute for Applied Health Research Berlin GmbH acted as subcontractor and
received funding from WIG2 GmbH for the execution of the study and medical
writing support.
Ingo Diel has received consulting fees for participation in advisory boards and has
given several presentations at speakers’ bureaus for Amgen.
Eugen Dornstauder is an Amgen employee and holds Amgen stock.
Robert Bartsch is an Amgen employee and holds Amgen stock.
Michael Kellner is an Amgen employee and holds Amgen stock.
Lennart Hickstein is an employee of InGef – Institute for Applied Health Research
Berlin GmbH and received funding from WIG2 GmbH for the execution of the
study and medical writing support
Josephine Jacob is an employee of InGef – Institute for Applied Health Research
Berlin GmbH and received funding from WIG2 GmbH for the execution of the
study and medical writing support.
David Hohmann was an Amgen employee during conduction of the analysis.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 13
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2018
Index
2018
262
Male and Female Breast Cancer: a Comparison of a 15-Year
Population-Based Cohort
Simone Schrodi 1; Michael Braun 2; Anne Andrulat 2; Sven Mahner 3;
Nadia Harbeck 3; Marion Kiechle 4; Stefan Paepke 4; Andreas Schnelzer 5;
Christian Schindlbeck 6; Ingo Bauerfeind 7; Claus Belka 8;
Stephanie E. Combs 9; Doris Mayr 10; Wilko Weichert 11; Jutta Engel 12
1Munich Cancer Registry (MCR), Bavarian Cancer Registry – Regional Centre
Munich (LGL) at the Institute of Medical Information Processing, Biometry and
Epidemiology (IBE), , München, Deutschland
2Red Cross Breast Centre, München, Deutschland
3Department of Gynecology and Obstetrics, Breast Centre, University Hospital,
LMU Munich, München, Deutschland
4Department of Obstetrics and Gynecology, University Hospital, Technical
University Munich, München, Deutschland
5Department of Obstetrics and Gynecology, RoMed Kliniken, Breast Centre,
Rosenheim, Deutschland
6Department of Obstetrics and Gynecology, Breast Centre, Klinikum Traunstein,
Traunstein, Deutschland
7Klinikum Landshut, Breast Centre, Landshut, Deutschland
8Department Radiation Oncology, University Hospital, LMU Munich, München,
Deutschland
9Department Radiation Oncology, Technical University Munich, München,
Deutschland
10Department of Pathology, LMU Munich, München, Deutschland
11Department of Pathology, Technical University Munich, München,
Deutschland
12Munich Cancer Registry (MCR), Bavarian Cancer Registry – Regional Centre
Munich (LGL) at the Institute of Medical Information Processing, Biometry
and Epidemiology (IBE), University Hospital, Munich, Germany, München,
Deutschland
Purpose: e aim was to compare prognostic factors, treatment, and out-
come of male and female breast cancer patients.
Methods: A total of 467 men and 58,484 women diagnosed with breast
cancer between 2002 and 2016 in the catchment area of the Munich Can-
cer Registry (MCR) were included in this analysis. A descriptive analy-
sis of prognostic factors and treatment, a comparison of outcome using
the Kaplan-Meier method, cumulative incidence (CI) in consideration of
competing risks and multivariate Cox regression analysis were conducted.
Results: At the time of diagnosis aected men were about 5 years older
than women (mean age 68 vs. 63 years). e proportion of T3/4- tumors
(16% vs.11%), positive lymph nodes (45% vs. 36%), and primary metasta-
ses (9% vs. 7%) was higher in men. Biologically, 99% of male tumors were
endocrine sensitive (vs. 87%) and 6% were HER2/neu positive (vs. 15%).
Men underwent more mastectomies (90% vs. 27%) and less radiotherapy
(44% vs. 71%). Frequencies of axillary surgery, chemotherapy, and endo-
crine therapy were not statistically dierent.
e time to local recurrence (TTL) was also similar in both groups. e
CI in time to metastasis (TTM) was higher in men (12% vs. 8% aer 5
years), however this dierence was not statistically signicant. Respective
multivariate cox-regression analysis also showed no signicant gender
dierences.
Survival improved slightly between 2002-2008 and 2009-2016, but only in
female patients. Survival was lower in men than in women, and this dif-
ference was greater for overall survival (OS) than for relative survival (RS)
(10-year-OS: 56% vs. 70%; 10-year-RS: 78% vs. 81%). Aer adjusting for
prognostic factors, the univariate hazard ratio declined from 1.8 (95%-CI
1.5-2.1) to 1.3 (1.1-1.5).
Conclusions: Probably, delayed diagnosis of breast cancer in male pa-
tients lead to a more advanced tumor stage. Aer adjusting for prognostic
factors, TTM was similar, whereas a statistically signicant dierence in
OS remained. Whether this nding is attributable to dierences in health/
lifestyle/other factors remains to be seen.
269
When Breast Cancer Wants to Spread, Suppress CYR61/CCN1
Johanna Hellinger; Hüchel Silke; Lena Goetz; Gerd Bauerschmitz;
Günter Emons; Carsten Gründker
UMG, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Deutschland
Purpose: Matricellular proteins modulate tumor micro environment and
are recognized to contribute to tumor cell invasion and dissemination.
CYR61, member of the CCN family of matricellular proteins, is upreg-
ulated in mesenchymal transformed and invasive breast cancer cells and
correlates with poor prognosis of breast cancer patients. Yet the signaling
whereby cancer cells gain invasive properties with regards to the epitheli-
al-mesenchymal transition (EMT) needs further research.
Methods: Mesenchymal transformed breast cancer cell lines were gen-
erated using prolonged mammosphere cultivation. Microarray analysis,
quantitative PCR and immune/histochemical approches were used to
analyze gene expression alterations upon CYR61 expression regulation
in 4 highly invasive breast cancer cell lines. Transient gene silencing was
conducted using RNA interference. Proliferation was assessed using Ala-
marBlue Assay. To examine the prognostic value of CYR61 and S100A4
expression in 239 patient samples immune-histochemical analysis were
performed.
Results: We investigated the use of CYR61 as a therapeutic target and
prognostic marker for invasive breast cancer and metastasis. Our data in-
dicates that CYR61 regulates metastasis-associated protein S100A4. Sup-
pression of CYR61 reduces the expression of S100A4 through changes in
ERK1/2 activation. Treatment with extracellular CYR61 increased tumor
cell invasion of non-invasive breast cancer cells. Immune-histochemical
analysis of 239 patient tissue samples revealed that higher CYR61 and
S100A4 expression correlates with invasive breast cancer and metastasis.
Conclusions: Our data suggest that CYR61 regulates cancer cell invasion
in highly invasive and aggressive breast cancer cells by altering S100A4 ex-
pression. ese ndings identify mechanism by which CYR61 suppresses
cell invasion and suggest it to be a potential therapeutic target and prog-
nostic marker for invasive breast cancer and metastasis.
Disclosure Statement: e authors declare no disclosures.
270
Palbociclib Plus Fulvestrant as First-Line Therapy for Patients
with Locally Advanced, Inoperable or Metastatic HR+/HER2-
Breast Cancer in Germany: Interim Results of the Inge-B Phase
2 Study
Anja Welt 1; Manfred Welslau 2; Diana Lüftner 3; Mustafa Deryal 4;
Rüdiger Liersch 5; Jörg Sahlmann 6; Leonora Houet 6; Karin Pottho 6;
Norbert Marschner 7; Corinne Vannier 6
1Universitätsklinikum Essen, Innere Klinik, Essen, Deutschland
2MVZ, Klinikum Aschaenburg, Aschaenburg, Deutschland
3Charité, Campus Mitte, Berlin, Deutschland
4Caritasklinik St. Theresia, Frauenheilkunde, Saarbrücken, Deutschland
5Hämatologisch-Onkologische Gemeinschaftspraxis, Münster, Deutschland
6iOMEDICO AG, Freiburg, Deutschland
7Praxis für Interdisziplinäre Onkologie, Freiburg, Deutschland
Purpose: In the PALOMA-3 trial, palbociclib plus fulvestrant demon-
strated a clinically meaningful improvement in overall survival compared
with fulvestrant plus placebo in patients (pts) with hormone receptor-pos-
itive (HR+), HER2-negative (HER2-) metastatic breast cancer who had
relapsed or progressed on prior endocrine therapy (Turner NC et al.,
NEJM 2018). Detailed analyses for rst-line (1L) and later- line (2L+)
therapy are still limited.
Methods: e prospective, multicenter phase 2 INGE-B trial was designed
to generate ecacy and safety data on the combination of palbociclib with
aromatase inhibitors or fulvestrant (1L, 2L+). is pre-planned interim
analysis was conducted to evaluate data on pts receiving palbociclib plus
fulvestrant as 1L or 2L+ therapy. e primary objective was the clinical
benet rate (CBR) in pts with measurable disease according to RECIST
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2018
Index
2018
v1.1. Key secondary endpoints included the overall response rate (ORR),
the CBR for all pts, and safety. Data were analyzed with descriptive
statistics.
Results: At the cut-o date of the interim analysis (Dec 17, 2018), 124
pts have been recruited to receive palbociclib plus fulvestrant (1L: 57 pts;
2L+: 67 pts). Of those, 54 pts treated in 1L were evaluable. Median age
was 69.5 years, 96.3% of pts had an ECOG performance score of 0 or 1.
31.5% (n=17) of pts had non-measurable bone-only disease. e CBR was
58% (n=21) for the 36 pts with measurable disease (RECIST v1.1) and
65% (n=35) for all pts (investigator assessment). Grade 3/4 adverse events
experienced by at least 10% of pts were neutropenia (n=17, 31.5%) and
leukopenia (n=8, 14.9%).
Conclusions: is INGE-B interim analysis showed for the rst time a
remarkable clinical benet for palbociclib plus fulvestrant as rst-line
therapy for pts with HR+/HER2- advanced breast cancer. No new safety
signals emerged.
Reference:
1. Welt A et al., Annals of Oncology (2019) 30 (suppl_3)
Disclosure Statement: AW, Advisory Boards: AstraZeneca, Novartis, Roche, Eisai,
Pzer, Amgen, Lilly; Fees: COCS GmbH, iOMEDICO AG, Interplan AG; Funding
of scientic programs: Novartis. DL, Member of Advisory Board with Amgen,
Novartis, Eli Lilly, Pzer, Celgene and Astra Zeneca; Corporate-sponsored research
by Novartis. MW, Advisory board or board of directors: Amgen, Bristol-Myers
Squibb, Celgene, GILEAD, HEXAL, Janssen, Lilly, medac, NOVARTIS, Roche,
SANOFI; Corporate-sponsored research with AMGEN, Astellas, Astra Zeneca,
Celgene, GILEAD, HEXAL, Janssen, Lilly, NOVARTIS, Roche. NM, Employ-
ment or Leadership Position: iOMEDICO, Stockholder Ownership: iOMEDICO,
Financing of Scientic Research: Pzer
272
Palbociclib Plus Fulvestrant as Second- or Later-Line Therapy
for Patients with Locally Advanced, Inoperable or Metastatic
HR+/HER2- Breast Cancer in Germany: Interim Results of the
Inge-B Phase 2 Study
Diana Lüftner 1; Manfred Welslau 2; Rüdiger Liersch 3; Mustafa Deryal 4;
Cosima Brucker 5; Jaqueline Rauh 6; Anja Welt 7; Matthias Zaiss 8;
Jörg Sahlmann 9; Leonora Houet 9; Corinne Vannier 9; Karin Pottho 9;
Norbert Marschner 8
1Charité, Campus Mitte, Berlin, Deutschland
2MVZ, Klinikum Aschaenburg, Aschaenburg, Deutschland
3Hämatologisch-Onkologische Gemeinschaftspraxis, Münster, Deutschland
4Caritasklinik St. Theresia, Saarbrücken, Deutschland
5Klinikum Nürnberg, Nürnberg, Deutschland
6Gemeinschaftspraxis Innere Medizin, Witten, Deutschland
7Universitätsklinikum Essen, Essen, Deutschland
8Praxis für Interdisziplinäre Onkologie, Freiburg, Deutschland
9iOMEDICO AG, Freiburg, Deutschland
Purpose: In the PALOMA-3 trial, palbociclib plus fulvestrant demon-
strated a clinically meaningful improvement in overall survival compared
with fulvestrant plus placebo in patients (pts) with hormone receptor-pos-
itive (HR+), HER2-negative (HER2-) metastatic breast cancer who had
relapsed or progressed on prior endocrine therapy (Turner NC et al.,
NEJM 2018). Detailed analyses for rst-line (1L) and second- or later- line
(2L+) therapy are still limited.
Methods: e prospective, multicenter phase 2 INGE-B trial was designed
to generate ecacy and safety data on the combination of palbociclib with
aromatase inhibitors or fulvestrant (1L, 2L+). is pre-planned interim
analysis was conducted to evaluate data on pts receiving palbociclib plus
fulvestrant as 1L or 2L+ therapy. e primary endpoint was the clinical
benet rate (CBR) in pts with measurable disease according to RECIST
v1.1. Key secondary endpoints included the overall response rate (ORR),
the CBR for all pts, and safety. Data were analyzed with descriptive
statistics.
Results: At the cut-o date of the interim analysis (Dec 17, 2018), 124
pts have been recruited to receive palbociclib plus fulvestrant (1L: 57 pts;
2L+: 67 pts). 57 of 67 pts treated in 2L+ were evaluable. Median age was
68.0 years, 91.2% (n=52) of pts had an ECOG performance score of 0 or
1. 28.1% (n=16) of pts had non-measurable bone-only disease. e CBR
was 35% (n=14) for the 40 pts with measurable disease (RECIST v1.1) and
51% (n=29) for all pts (investigator assessment). Grade 3/4 adverse events
experienced by at least 10% of pts were neutropenia (n=21, 36.8%) and
leukopenia (n=7, 12.3%).
Conclusions: is INGE-B interim analysis showed a remarkable clinical
benet for palbociclib plus fulvestrant as second- or later-line therapy for
pts with HR+/HER2- advanced breast cancer. No new safety signals were
detected.
Reference:
1. Lüner D et al., ESMO 2019, #1423
Disclosure Statement: DL, Advisory board or board of directors: Amgen, Eli Lilly,
Celgene, Novartis, Pzer, Teva, Tesaro, Loreal, MSD, Astra Zeneca; Corporate-
sponsored research with Amgen, Novartis; MW, Advisory board or board of
directors: Amgen, Bristol-Myers Squibb, Celgene, GILEAD, HEXAL, Janssen,
Lilly, medac, NOVARTIS, Roche, SANOFI; Corporate-sponsored research with
AMGEN, Astellas, Astra Zeneca, Celgene, GILEAD, HEXAL, Janssen, Lilly,
NOVARTIS, Roche, SANOFI; AW, Advisory board or board of directors: Roche,
Novartis, AstraZeneca, Lilly, Eisai, Pzer, Amgen; Corporate-sponsored research:
Novartis (scientic grant);NM, Employment or Leadership Position: iOMEDICO,
Stockholder Ownership: iOMEDICO, Financing of Scientic Research: Pzer
300
Long-Term Adjuvant Therapies for Breast Cancer are
Over-Treatments
Dieter Hölzel 1; Gabriele Schubert-Fritschle 2; Jutta Engel 2
1Tumorregister München Ludwig-Maximilians-Universität, München,
Deutschland
2Tumorregister München, Ludwig-Maximilians-Universität, München,
Deutschland
Purpose: Breast cancer guidelines recommend adjuvant endocrine ther-
apies (EAT) for 10 years because randomized trials with tamoxifen im-
proved survival by 2.8% aer 15 years. However, there is no convincing
reason for a long duration of treatment.
Methods: ese ndings are based on known facts and studies on inci-
dence, growth and diagnosis of primary breast cancer (PT) and its metas-
tases (MET). Many studies have shown the eect of neoadjuvant and ad-
juvant therapies on manifest and occult PTs and their METs. When these
therapies are shortened, prolonged, delayed or interrupted inconsistencies
between eects, duration of treatment and treatment windows arise.
Results: e survival benet of EATs is real, but EATs are not evi-
dence-based. Extensions aer 1, 2 or 5 years have no eect on surviv-
al for 5 years each, although 49%, 42% or 28% of all METs occur at
these intervals. If therapies are delayed by months or years, the ef-
fects are comparable to those of primary treatment without delay,
but all METs expected without therapy appear in the delay phase.
e 2.8% eect is achieved by “chemoprevention, the neoadjuvant treat-
ment of ipsilateral and contralateral occult second malignancies, which
eradicate 50% and with them about 25% of their expected METs. e
eect size is determined by the higher risk of secondary breast cancers.
But for the duration of the prevention of 5 years, there are no convincing
explanations. Due to the slow growth of the PTs and the large treatment
window, in which newly emerging up to almost detectable PTs are rapidly
eradicated, these EATs can be interrupted without disadvantage and the
therapy can be signicantly de-escalated.
Conclusions: From known facts can be deduced: Intermittent therapies
can reduce long-term therapies by 70-80% with equal eect. Less side ef-
fects with a higher quality of life and better survival rates through higher
compliance would be a therapy innovation for almost one million breast
cancer patients in Germany alone. e challenge for optimal duration is:
how short is short enough.
Disclosure Statement: No conict of interest.
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2018
310
Circulating Non-Coding RNA – Biomarker Potential in
Neoadjuvant Chemotherapy of Triple Negative Breast Cancer?
Marc Hirschfeld 1, 2, 3; Andrea Ritter 1, 2; Kai Berner 1, 2; Gerta Rücker 4;
Markus Jäger 1, 2; Daniela Weiß 1, 2; Markus Medl 1, 2; Claudia Nöthling 1, 2;
Sandra Gassner 1, 2; Jasmin Asberger 1, 2; Thalia Erbes 1, 2
1Department of Obstetrics and Gynecology, Medical Center – University of
Freiburg, Freiburg, Deutschland
2Faculty of Medicine, University of Freiburg, Freiburg, Deutschland
3Institute of Veterinary Medicine, Georg-August-University Goettingen,
Goettingen, Deutschland
4Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical
Center - University of Freiburg, Freiburg, Deutschland
Purpose: Early response to neoadjuvant chemotherapy (NACT) is highly
associated with benecial outcome in breast cancer (BC) patients espe-
cially in triple negative (TNBC) and Her2 enriched molecular subtypes.
Non-coding RNAs (ncRNAs) such as microRNAs (miR) are involved in
carcinogenesis and cell proliferative processes where they can act either
as tumor suppressors or as oncogenes. Liquid biopsy-based ncRNA bio-
markers might represent valuable innovative tools in the prediction of
NACT response of TNBC patients improving patients’ outcome.
Methods: One triple positive (BT-474) and three triple negative (BT-20,
HS-578T, MDA-MB-231) breast cancer cell lines were treated with cyto-
static drugs (carboplatin, epirubicin, gemcitabine and paclitaxel). Intra-
and extracellular evaluation of 12 microRNAs, 1 piRNA and 1 tRNA ex-
pression proles were performed by extracellular vesicular RNA-isolation
and subsequent qRT-PCR. Relative quantication was performed accord-
ing to Busk et al. 2014. Eight TNBC patients as well as ten healthy women
provided serum and urine specimen. ncRNA expression level comparison
was performed applying two-sample t-test. Preliminary, samples of TNBC
patients were compared at two time points.
Results: Distinct ncRNA expression alterations in (TN)BC cell lines in
both the intra- and extracellular compartment were observed aer che-
motherapeutic treatment. Serum and urine-based ncRNA expression
identied as applicable tool to discriminate TNBC vs. controls. Time
point comparison of TNBC urine samples revealed a general ncRNA rise.
Serum data identied diversely, implying a potential correlation with an
NACT-driven clinical complete response.
Conclusions: is study provides new insights into the involvement of a
BC-related ncRNA panel in the response of TNBC to NACT both in vitro
and in vivo. On the one hand, distinct ncRNA expression proles could
help to improve TNBC diagnosis. On the other hand, monitoring of se-
rum or urine ncRNA levels mightt contribute to TNBC therapy response
management with the goal of improving patients` outcome.
328
Monarch 2: Interim Overall Survival of Abemaciclib Plus
Fulvestrant in Patients with HR+, HER2Advanced Breast
Cancer
Eva Maria Grischke 1; George W Sledge 2; Masakazu Toi 3; Patrick Neven 4;
Joo Hyuk Sohn 5; Kenichi Inoue 6; Xavier Pivot 7; Olga Burdaeva 8;
Norikazu Masuda 9; Peter Kaufman 10; Han Koh 11; Pierfranco Conte 12;
Susana Barriga 13; Karla Hurt 13; Martin Frenzel 13; Stephen Johnston 14;
Antonio Llombart-Cussac 15
1Tübingen, Universität Tübingen, Tübingen, Deutschland
2Stanford, Stanford University School of Medicine, Stanford, United States
3Präfektur Kyōto, Graduate School of Medicine, Japan
4Löwen, Universitaire Ziekenhuizen Leuven, Löwen, Belgien
5Seoul, Yonsei Cancer Center, Seoul, Südkorea
6Präfektur Saitama, Saitama Cancer Center, Japan
7Straßburg, Centre Paul Strauss, Straßburg, Frankreich
8Archangelsk, Arkhangelsk Regional Clinical Oncology Dispensary, Archangelsk,
Russland
9Ōsaka, NHO Osaka National Hospital, Ōsaka, Japan
10Burlington, University of Vermont Cancer Center, Burlington, United States
11Bellower, Kaiser Permanente, Bellower, Bellower, United States
12Padua, University of Padova, Padua, Italien
13Indianapolis, Eli Lilly and Company, Indianapolis, United States
14London, The Royal Marsden NHS Foundation Trust, London, United Kingdom
15Valencia, Hospital Arnau Vilanova, Valencia, Spanien
Purpose: In MONARCH 2, abemaciclib+fulvestrant signicantly im-
proved progression-free survival (PFS) vs placebo+fulvestrant (median:
16.4 vs 9.3 months, HR: 0.553) with a tolerable safety prole.
Methods: MONARCH 2 was a global, randomized, double-blind phase3
trial of abemaciclib+fulvestrant (N=446) or placebo+fulvestrant (N=223)
in women with advanced endocrine therapy (ET)-resistant hormone re-
ceptor-positive (HR+), human epidermal growth factor receptor 2-neg-
ative (HER2-) advanced breast cancer (ABC). ET resistance was dened
as progression on (neo)adjuvant ET, or ≤12 months from end of adju-
vant ET, or on rst-line ET for metastatic BC. Patients with measurable
disease (per RECIST v1.1) or nonmeasurable bone-only disease and any
menopausal status were included (pre- or perimenopausal women also
received a gonadotropin-releasing hormone agonist). Prior chemotherapy
was permitted only in (neo)adjuvant setting. 669 patients were random-
ized 2:1, stratied based on nature of disease (visceral, bone-only, or other
metastases) and resistance to prior ET (primary vs secondary). Abemac-
iclib or placebo 150mg was dosed Q12H, and fulvestrant 500mg was ad-
ministered per label. e primary objective was investigator-assessed PFS.
OS is an important secondary endpoint. e family-wise type I error is
controlled at 0.025 (1-sided), with a gate-keeping strategy between PFS
and OS. For OS, an α-spending function will be used to account for in-
terim and nal analyses. OS will be compared using a 1-sided stratied
log rank test.
Results: e preplanned interim OS analysis at approximately 331 events
will be conducted and presented at the meeting.
Conclusions: Following the preplanned interim OS analysis, the associat-
ed conclusions will be presented at the meeting.
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2018
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2018
330
Monarcher: A Randomized Phase 2 Study of Abemaciclib Plus
Trastuzumab with or without Fulvestrant Versus Trastuzumab
Plus Standard-of-Care Chemotherapy in Women with HR+,
HER2+ Advanced Breast Cancer
Johannes Ettl 1; Sara Tolaney 2; Andrew Wardley 3; Stefania Zambelli 4;
John F Hilton 5; Francesco Ricci 6; Seock-Ah Im 7; Sung-Bae Kim 8; Stephen
Johnston 9; Arlene Chan 10; Shom Goel 11; Kristen Catron 12; Zhengyu Yang 12;
Corona Gainford 12; Fabrice Andre 13
1München, Technische Universität, München, Deutschland
2Boston, Harvard University, Boston, United States
3Manchester, University of Manchester, Manchester, United Kingdom
4Mailand, IRCCS Ospedale San Raaele, Mailand, Italien
5Ottawa, The Ottawa Hospital and University of Ottawa, Ottawa, Kanada
6Paris, Institute Curie, PSL Research University, Paris, Frankreich
7Seoul, Seoul National University College of Medicine, Seoul, Südkorea
8Seoul, Asan Medical Center, Seoul, Südkorea
9London, Royal Marsden Hospital, London, United Kingdom
10Nedlands, reast Cancer Research Centre - WA and Curtin University, Nedlands,
Australien
11Boston, Dana-Farber Cancer Institute, Boston, United States
12Indianapolis, Eli Lilly and Company, Indianapolis, United States
13Villejuif, Université Paris Sud, Villejuif, Frankreich
Purpose: Abemaciclib showed ecacy and tolerability in patients (pts)
with HR+, HER2- advanced breast cancer (ABC). In preclinical models,
inhibition of CDK4 by abemaciclib enhanced the activity of HER2-direct-
ed agents and re-sensitized resistant tumors to HER2 blockade, suggesting
a crosstalk between HER2 signaling and the cyclin D1/CDK4 signaling
pathways in HER2+ BC.We report the eect of abemaciclib in pts with
HR+, HER2+ ABC.
Methods: monarcHER is a Phase 2 study comparing the ecacy of abe-
maciclib (150mg PO Q12H on Days 1-21 of a 21-day cycle)+trastuzumab
(IV infusion on Day 1 of 21-day cycle) with fulvestrant (F; 500mg IM on
Cycle 1 D1 and D15 and Cycle 2 D8, then Q4W; Arm A) or without F
(Arm B) vs trastuzumab+standard-of-care chemotherapy (per label on
21-day cycle; Arm C) in pts with HR+, HER2+ ABC. Eligible pts were
postmenopausal women with ≥2 HER2-directed therapies for advanced
disease and received prior T-DM1 and taxane in any disease setting,
had ECOG PS ≤1, and LVEF ≥50%. 237 pts were randomized 1:1:1 and
stratied based on the number of prior systemic regimens (excluding sin-
gle-agent ET) for ABC (2 to 3 vs 3+) and nature of the disease (measurable
vs nonmeasurable). Primary objective was to compare the PFS of Arm A
and B to Arm C. Secondary objectives included OS, response evaluation,
safety, ecacy, and pharmacokinetics. e primary analysis was planned
at ~165 PFS events, providing 80% statistical power to detect superiority
of Arm A over Arm C, assuming a HR of .667 at 1-sided α=.1.
Results: e monarcHER study was conducted in 14 countries. e last
patient entered treatment on February 28, 2018. e data from the prima-
ry analysis for ecacy and safety will be available mid-May 2019.
Conclusions: e conclusion for PFS, objective response rate (complete
response [CR]+partial response [PR]), disease control rate (CR+PR+stable
disease [SD]), clinical benet rate (CR+PR+SD ≥6 months) and safety
data will be presented at the meeting.
363
Secretome Analysis Reveals Driver for Bone-Directed Breast
Cancer Invasion
Johanna Hellinger 1; Franziska Schömel 1; Christof Lenz 2, 3;
Gerd Bauerschmitz 1; Günter Emons 1; Carsten Gründker 1
1UMG, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Deutschland
2Max-Planck-Institut für biophysikalische Chemie, Bioanaltytical Mass
Spectrometry Group, Göttingen, Deutschland
3UMG Institute of Clinical Chemistry, Core Facility Proteomics, Göttingen,
Deutschland
Purpose: e tumour metastatic cascade is highly regulated by the mi-
cro environmental changes. Drugs are needed to modify the breast micro
environment, where tumour cells gain the ability to disseminate. Here we
suggest potential drivers of initial dissemination of tumour cells with re-
gards to bone-directed metastasis. While an increased CTGF expression
in human breast cancer correlates with poor patient outcome and drug
resistance (1), a major questions has remained: Will targeting CTGF help
to prevent breast cancer cell dissemination into the surrounding tissue?
And which underlying molecular mechanisms are involved in breast can-
cer directed bone metastasis?
Methods: Here, we apply secretome analysis, proteome analysis and mi-
croarray data to elucidate drivers of epithelial-mesenchymal transition
and cell invasion. Gene ontolgy enrichment analysis led us to the prom-
inent regulated pathways. To examine in vitro invasive properties we as-
sessed 2D invasion in a modied boyden chamber, 3D spheroid invasion,
cell-ECM adhesion and ECM degradation.
Results: CTGF is highly upregulated when MCF-7 non-invasive breast
cancer cells are co-cultured with osteosarcoma cells and gain invasive
properties. Suppression of CTGF reduced invasion and expression of
EMT-related genes. GnRH agonist Triptorelin reduces CTGF expression
in a RhoA -dependent manner.
Conclusions: Our data indicate a mechanism by which extracellular
CTGF drives cell dissemination by regulating cell adhesion, ECM degra-
dation and regulation of EMT inducing factor TGFBI. Moreover it was as-
sessed that CTGF expression is regulated by RhoA activity. e performed
experiments support the value of CTGF as therapeutic target for invasive
breast cancer, and GnRH agonist Triptorelin treatment could be of value
in clinical applications.
Reference:
1. Wells JE, Howlett M, Cole CH, Kees UR. Deregulated expression of connective
tissue growth factor (CTGF/CCN2) is linked to poor outcome in human
cancer. International Journal of Cancer. 2015;137(3):504-11.
Disclosure Statement: e authors declare no disclosures.
378
Micrometastases in Axillary Lymph Nodes and Outcome
of Breast Cancer
Madeleine Hetterich 1; Michael Gerken 2; Olaf Ortmann 1;
Monika Klinkhammer-Schalke 2; Atanas Ignatov 1
1Department of Obstetrics and Gynecology, University Medical Center
Regensburg, Regensburg, Deutschland
2Tumor Center Regensburg, Institute for Quality Assurance and Health Services
Research, University of Regensburg, Regensburg, Deutschland
Purpose: e axillary lymph node status is one of the most important
prognostic factors in patients with primary breast cancer. Micrometas-
tases (pN1mi) are dened as nodal metastases with deposits from >0.2 ≤
2mm. eir impact on overall survival (OS) and recurrence-free survival
(RFS) of patients with breast cancer remains unclear. ere are no rec-
ommendations concerning the performance of adjuvant chemotherapy.
us, the aim of this study was to analyze the eect of micrometastases
on the clinical outcome of patients with breast cancer according to their
adjuvant chemotherapy status.
Methods: We performed a retrospective registry-based study. 26353 pa-
tients were investigated and 14070 were excluded and 12283 were eligible
for analysis: 11743 were identied as pN0 and 540 as pN1mi.
Results: Micrometastases in regional lymph nodes were associated with a
reduced 10-year rate of OS and RFS among women with early-stage breast
cancer, who did not receive systemic adjuvant chemotherapy. e eect
however, was not conrmed in the multivariate analysis aer adjustment
for age, tumor size, grading (etc.). Furthermore, in the group of patients
with micrometastases systemic treatment improved neither the OS (haz-
ard ratio (HR) 1.51, 95% condence interval (CI) 0.80-2.85) (p=0.208)
nor the RFS (HR 1.12, 95%CI 0.63-1.97) (p=0.705) as demonstrated by
multivariate cox-regression analysis.
Conclusions: Chemotherapy did not improve signicantly the outcome
of breast cancer patients with nodal micrometastases. In this regard, nodal
micrometastases should not be considered in our treatment decision.
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2018
Index
2018
Reference:
1. De Bowe et al.: Micrometastases or Isolated Tumor Cells and the Outcome of
Breast Cancer. NEJM. August 13, 2009.
412
Evidence-Based Decision Support System for Breast Cancer
Michael Dück 1; Eberhard Beck 1
1Technische Hochschule Brandenburg, Fachbereich Informatik und Medien,
Brandenburg an der Havel, Deutschland
Purpose: In order to increase the patients’ ability to make their own in-
formed decisions about their breast cancer therapy and to support patient
empowerment in general, it is necessary to provide decision-relevant in-
formation in an understandable mode. is aim will be targeted by gen-
erating computer-based systems which provide the relevant information
resulting in guideline-based decisions.
Methods: By using the evidence-based guidelines for the treatment of
breast cancer1,2 a web-based decision support platform for patients and
health care professionals is being created. e design and content will be
kept up-to-date by involving the target groups in the development.
Results: Two prototypes for an evidence-based decision support platform
were created to test if it was possible to translate the medical guidelines
to a digital rule-based system, which is able to create relevant suggestions
based on the information given by a patient. ose prototypes were eval-
uated by a patient and a health care professional and will be continuously
improved and tested.
Conclusions: e rst evaluations proofed that there is a need for patient
information systems, especially for diseases with a high risk for complica-
tions and a wide eld of treatment options. In order to improve the quality
of shared decision making and thus increase the patients’ compliance with
selected treatment choices, these systems could support the patients by
increasing this decease-related knowledge. e continuous development
and evaluation of evidence-based decision support systems for breast
cancer patients and for other malignant or chronic diseases is one of our
major goals.
References:
1. Interdisziplinäre S3-Leitlinie für die Früherkennung, Diagnostik, erapie und
Nachsorge des Mammakarzinoms, Albert, U, et al.
2. Diagnostik und erapie früher und fortgeschrittener Mammakarzinome,
Janni, W, et al.
Disclosure Statement: e author declares that he has no relevant or material
nancial interests that relate to the research described in this paper
461
Panel-Guided Personalized Medicine in Metastatic Breast and
Gynecological Cancer, First Experiences at te CCC Munich LMU
Elena Sultova 1; Benedikt Westphalen 2; Andreas Jung 3; Thomas Kirchner 3;
Doris Mayr 3; Volker Heinemann 2; Klaus Metzeler 2; Philipp Greif 2;
Fabian Trillsch 4; Sven Mahner 4; Nadia Harbeck 1; Rachel Würstlein 1
1LMU Munich, University Hospital, Department of Obstetrics and Gynecology,
Breast Center and CCC Munich LMU, München, Deutschland
2Klinikum der Universität München , Medizinische Klinik und Poliklinik III und
CCC Munich LMU, München, Deutschland
3Ludwig-Maximilians-Universität München, Pathologisches Institut der LMU
und CCC München LMU, München, Deutschland
4LMU Munich, University Hospital, Department of Obstetrics and Gynecology,
CCC Munich LMU, München, Deutschland
Purpose: Some tumorigenic alterations associated with cancer cell devel-
opment and progression can be therapeutically addressed by molecularly
targeted agents. Comprehensive genomic proling identifying such ac-
tionable alterations aims to oer personalized treatment to cancer patients.
Here, we report rst experiences of the Comprehensive Cancer Center
Munich Molecular Tumor Board (MTB) in breast and gynecologic malig-
nancies. Our aim was to measure the impact of recommendations made
by a multidisciplinary tumor board on the overall survival of patients with
gynecologic cancers, that progressed under standard treatment.
Methods: 99 patients diagnosed with metastatic breast or gynecologic
malignancies underwent molecular diagnostic test (panel). From May
2017 through March 2019, our MTB reviewed the clinical cases carefully
considering tumor prole and discovered genetic aberrations and provid-
ed further diagnostic and therapy recommendations. All patients were
part of a prospective registry (Der informative Patient).
Results: 95 patients with metastatic gynecologic tumors were discussed
in the MTB (68% breast cancers, 20% ovarian cancer, 5% cervical cancer,
3% endometrial cancer and 4% others). e genes with the highest muta-
tion rate were PI3KCA, KRAS, FGFR1 and CCND1. Overall, 34 patients
(36%) received an alteration-specic targeted therapy recommendation.
Recommended therapies included various drugs such as protein-kinase
inhibitors (45%), combination therapies (24%) and clinical trials (20%).
erapeutic recommendations were implemented in 9 cases; 4 patients
experienced a clinical benet with a partial response or stabilization last-
ing over 4 months, including 3 of them receiving o-label treatment.
Conclusions: In the setting of a multidisciplinary molecular tumor board,
a small but clinically meaningful group of breast and gynecologic can-
cer patients derives benet from comprehensive genomic proling. Main
problems of precision cancer medicine include patients’ referral at late
stage disease and limited access to targeted agents.
470
Recommendation of Trastuzumab Therapy for Patients with
Non-Metastatic, HER2/NEU-Positive Breast Cancer: Results
from 3,052 Patients Treated in Certied German Breast Cancer
Centres
Nora Tabea Sibert 1; Christoph Kowalski 1; Clara Breidenbach 1;
Julia Ferencz 2; Sebastian Dieng 2; Elisabeth C. Inwald 3;
Simone Wesselmann 1; Olaf Ortmann 3 and the German Breast Cancer
Centres Participating in the Oncobox Research Project 4
1Deutsche Krebsgesellschaft e.V., Zertizierung, Berlin, Deutschland
2OnkoZert GmbH, Neu-Ulm, Deutschland
3University Medical Center Regensburg, Department of Gynecology and
Obstetrics, Regensburg, Deutschland
Purpose: Since 2006 it is possible to treat non-metastatic, Her2/neu-pos-
itive breast cancer (BC) patients with Trastuzumab in Germany which is
now a highly accepted therapy strategy. Even if the treatment of Her2/
neu-positive BC patients with Trastuzumab is part of the quality indicator
9 of the evidence-based German Guideline for Breast Cancer (S3), recent
studies highlight that there are some Her2/neu-positive BC patients for
whom physicians do not recommend a Trastuzumab therapy (TT). We
investigate for which patients a TT is recommended in Breast Cancer
Centers (BCC) certied by the German Cancer Society and the German
Society for Senology.
Methods: We included Her2/neu-positive, non-metastatic BC patients
(≥ pT1c) treated in German BCCs by surgery between 2006 and 2019. For
3,052 patients, data collected for the certication progress including more
than 150 attributes specifying clinical and treatment characteristics for
each patient were available. A multi-level analysis including these 3,052
patients nested in 17 BCCs was performed.
Results: Recommendation of TT does not dier much between BCCs
(ICC null model: 0.14). Our analysis show that physicians in BCCs more
oen recommend TT to patients who are younger than 69 years and who
had another oncological disease before. Patients with a recommendation
for any additional therapy (chemo-/endocrine therapy, radiation) to sur-
gery receive more likely a recommendation for TT as well (all p < 0.05), if
controlled for T- and N-stage, sex and estrogen- and progesterone-recep-
tor status. Furthermore, there is a signicant increase in recommendation
of TT over the years (frequency of recommendation of TT for patients
treated between 2006 and 2011: 43.4% vs. patients treated between 2012
and 2019: 78.7%).
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Conclusions: In certied German BCCs, the knowledge and acceptance
of guideline-adherent TT is increasing (positive cohort eect). Recom-
mendation of TT for Her2/neu-positive BC patients in BCCs are signi-
cantly associated to age and the recommendations for other additional
therapies apart from surgery.
487
Age-Related Dierences in Overall and Metastases-Free
Survival after Guideline Concordant Chemotherapy in
Patients with Hormone Receptor Positive and Nodal Positive,
Early Breast Cancer
Clara Taubenhansl 1; Olaf Ortmann 2; Michael Gerken 1;
Elisabeth C. Inwald 2; Monika Klinkhammer-Schalke 1
1Tumor Center, Institute for Quality Management and Health Services Research,
University of Regensburg, Regensburg, Deutschland
2Department of Obstetrics and Gynecology, University Medical Center
Regensburg, Caritas Hospital St. Josef Regensburg, Regensburg, Deutschland
Purpose: e German guideline for breast cancer recommends using che-
motherapy (CHT) in patients with hormone receptor positive and nodal
positive, invasive breast cancer. e aim of this study was to analyse the
eects of CHT in this patient group on overall survival (OS) and distant
metastases-free survival (DMFS), especially considering the 70-year
threshold.
Methods: 1772 patients from the clinical cancer registry Regensburg (Ger-
many) with hormone receptor positive and nodal positive, invasive breast
cancer diagnosed between 2003 and 2013 were analysed in a retrospective
cohort study. OS and DMFS were evaluated by means of Kaplan-Meier
and multivariable Cox-regression method. Results were further examined
according to age at diagnosis.
Results: e comparison of 1544 patients with CHT to 228 patients
without CHT showed a signicant benet for CHT regarding 5-years OS
(91.3% vs. 76.8%) and 5-years DMFS (86.7% vs. 74.4%, both p<0.001).
Likewise, better OS and DMFS were seen in patients ages <70 years using
CHT compared to patients without CHT of the same age. Patients ages
>=70 years with CHT had a minimal benet regarding 5-years OS com-
pared to patients without CHT, but no advantage considering DMFS. All
results were conrmed in multivariable analyses except for patients being
>=70 years of age.
Conclusions: Patients with hormone receptor positive and nodal posi-
tive, invasive breast cancer benet from chemotherapy with regard to a
signicantly better overall and distant metastases-free survival, although
chemotherapy use in patients ages >=70 years results in a smaller benet
considering OS and no benet considering DMFS.
Disclosure Statement: e authors declare no conict of interest.
504
Abus as an Alternative to Hand Held Ultrasound for Response
Control in Neoadjuvant Breast Cancer Treatment
Maria Eleni Hatzipanagiotou; Madeleine Hetterich; Blanca Roca Ripoll;
Tanja Eggensberger; Olaf Ortmann; Stephan Seitz
University medical centre Regensburg, Department of Gynecology and
Obstetrics , Regensburg, Deutschland
Purpose: e “Invenia Automated Breast Ultrasound Screening” (ABUS)
for automatic ultrasound examination is indicated as an adjunct to mam-
mography for breast cancer screening in asymptomatic women (approved
by the FDA), for whom screening mammography ndings are normal or
benign but have a high density of breast tissue. ABUS provides ecient
exam reading and analysis within 3 to 6 minutes on the work station (1).
e aim of this study is to evaluate the use of ABUS in patients who are
under neoadjuvant chemotherapy treatment for response control.
Methods: We conducted regular sonographic response check and ABUS
examination in 20 women who were under neoadjuvant chemotherapy
treatment. e hand-held sonography was performed with GE Voluson S8.
e tumor was measured in 3 dimensions. e last sonographic check
took place within the last 4 weeks before the end of chemotherapy. We
compared the hand held sonographic measurement and the ABUS mea-
surement with the size of the pathologic tumor.
Results: We found that there was no signicant dierence between tumor
measurements with hand held ultrasound or ABUS ultrasound in neoad-
juvant response control.
e average dierence from hand held sonographic ultrasound size to nal
pathological tumor size was 9,2 mm. e average dierence from ABUS
ultrasound size to nal pathological tumor size was 8,6 mm (p=0,3). e
median dierence between ABUS and hand held ultrasound tumor size
was 4,8mm.
Conclusions: ABUS seems to be a suitable method to conduct response
control in neoadjuvant breast cancer treatment. ABUS oers remarkable
time saving for physicians compared to handheld ultrasound and thus
should be considered for clinical practice.
Reference:
1. https://www.ge-ultraschall.com/invenia-abus/
Disclosure Statement: n/a.
531
WNT Signaling-Mediated Inhibition of Aromatase
Expression – A Possible Endocrine Model for Triple Negative
Breast Cancers
Alexander Kaiser 1, 2; Martin Schmidt 2; Otmar Huber 2
1Universitätsklinikum Jena - Klinik für Innere Medizin II - Abteilung Hämatologie
und Internistische Onkologie, Jena, Deutschland
2Universitätsklinikum Jena - Institut für Biochemie II, Jena
Purpose: Local biosynthesis by aromatase in breast adipose broblasts
(BAFs) is the most important source for estrogens in estrogen-receptor
positive breast cancers (BC). Triple-negative BC depend on other growth-
promoting signals, e.g. Wnt-signaling. In this study, we investigated the
hypothesis that WNT3a expression in triple-negative BC suppresses
aromatase expression in BAFs.
Methods: Eects of WNT3a and BC cell-conditioned medium (CM) on
BAFs were investigated by cell-proliferation tests, tritium water release and
qRT-PCR assays for aromatase activity and gene expression, respectively.
Protein expression was analyzed by western blotting. A combination of
reporter gene assays, site-directed mutagenesis, protein overexpression
and chromatin immunoprecipitation (ChIP) was used for analysis of tran-
scription factor-binding to dierent binding-sites.
Results: WNT3a and CM of triple-negative breast cancer cells (e.g.
MDA-MB231) increased cell growth and suppressed aromatase activity
and promoter I.3/II-driven gene-expression up to 90%. ree putative
Wnt-responsive elements (WREs) in the aromatase promoter were found.
Promoter activity was inhibited by overexpression of full-length T-cell fac-
tor (TCF)-4 in 3T3-L1 preadipocytes in reporter gene assays. Full-length
lymphoid enhancer-binding factor (LEF)-1 increased activity. However,
WNT3a-stimulation resulted in a loss of TCF-4-binding to WRE1 and
induced a switch of nuclear LEF-1 isoforms to a truncated variant. Over-
expression of truncated LEF-1 inhibited promoter I.3/II-activity. ChIP
revealed a WNT3a-induced replacement of TCF-4 by a LEF-1-variant on
WRE1 of the aromatase promoter I.3/II in BAFs. Switching of LEF-1 iso-
forms may involve canonical Wnt-signaling.
Conclusions: e mechanism described here may contribute to the loss
of estrogen responsibility in the etiology of triple-negative breast cancers.
Strong Wnt-ligand expression by tumors could suppress aromatase ex-
pression in surrounding BAFs.
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540
Impact of Cytotoxic Treatment on PDL1 Expression in Human
Breast Cancer Cell Lines
Peter Ugocsai; Eva-Maria Rom-Jurek; Olaf Ortmann; Stephan Seitz;
Gero Brockho; Anja-Kathrin Wege
Department of Gynecology and Obstetrics, University Medical Center
Regensburg, Regensburg, Deutschland
Purpose: e oncologic spectrum for the clinical application of check-
point inhibitors (CI) expands rapidly. Clinical trials with CI in breast
cancer (BC) report an overall response rate of up to 19% with durable
clinical responses and tolerable safety proles. Improved understanding
of the immunogenicity of BC under simultaneously applied therapies, e.g.,
cytotoxic treatments, would help to develop more individual therapeutic
strategies to further increase response rates.
Methods: We investigated the expression of PD-L1 on dierent types (tri-
ple negative, luminal-type and HER2-positive) of human BC cell lines and
evaluated the eect of standard chemotherapeutical agents (epirubicin
and paclitaxel) on PD-L1 expression in selected cell lines.
Results: We found greatly varying levels of PD-L1 expression within the
investigated BC cell lines. High PD-L1 expression was found in all three
TNBC- and two of three HER2-overexpressing cell lines. Luminal like tu-
mors seem to express low PD-L1 levels, without great variations. Epiru-
bicin treatment caused a decrease and paclitaxel treatment an increase in
PD-L1 expression in the TNBC MDA-MB-231 cells. In contrast, PD-L1
expression changed to a minor extent in the HER2-overexpressing SK-
BR-3 cell line when exposed to cytotoxic treatments.
Conclusions: e degree of PD-L1 expression among breast cancer cell
lines varies considerably. Our analyses revealed dierent cell type specic
responses to cytotoxic treatments. Furthermore, diverse chemotherapeu-
tic agents engender dissimilar PD-L1 expression changes within the same
cell line, which likely contribute to the varying clinical responses to CI.
Further studies are needed to identify the major mechanisms determining
the immunogenic alterations of BC under chemotherapy.
Disclosure Statement: no conict of interest
547
Prevalence of Critical Values of the Functional and Mental
Status ofBreast CancerPatients Before the Onset of Cancer
Therapy
Niklas Grusdat 1; Alexander Stäuber 1; Henry Schulz 1; Ralf Haase 1;
Marion Tolkmitt 2; Jens Schnabel 2; Birgit Schubotz 3; Dirk-Henrik
Zermann 4; Mark Heydenreich 4
1Chemnitz University of Technology, Professorship of Sports Medicine / Sports
Biology, Chemnitz, Deutschland
2DRK Krankenhaus Chemnitz-Rabenstein, Brustkrebszentrum, Chemnitz,
Deutschland
3Klinisches Krebsregister Chemnitz, Deutschland
4Vogtland-Klinik Bad Elster
Purpose: A reduced functional and mental status even before the cancer
therapy may indicate a worse prognosis for mortality or lower resilience
throughout the dierent stages of cancer treatment. e objective of this
study was to determine the frequency of breast cancer patients demon-
strating parameters of functional and mental status below predicted
threshold values [1-4].
Methods: Within the ‘Return’ study [5] 68 patients with rst diagno-
sis of breast cancer (58±11 yr) in UICC stage 0-IV (0=4.4%, IA=60.3%,
IIA=22.0%, IIB=8.8, IIIA=1.5%, IIIC=1.5%, IV=1.5%) were examined
prior to cancer therapy. Standardised assessment of functional status in-
cluded a handgrip strength test (HGS), 6-minute-walk-test (6MWT) and
BIA for detection of bioimpedance phase angle (pA). e mental status
was investigated using the HADS-A and HADS-D.
Results: 21% of patients presented HGS below individual critical cut-
o value (27.8±5.6 kg). 16% showed a critical pA (5.3±0.9°). In 63% of
patients there was a shorter individual predicted distance in the 6MWT
(470±95m). Clinically relevant (HADS-A and D Score >10) anxiety and
depression scores were diagnosed in 53% and 39% of patients respectively.
18% of breast cancer patients presented with a severe form of anxiety. 16%
were identied with severe symptoms of depression.
Conclusions: e data provides evidence for the occurrence of critical
prognostic values of functional and mental status in breast cancer patients
before cancer therapy. Potential risk factors suggest the adaptation and in-
dividualisation of medical treatment. In order to optimise the treatment,
routine assessments are necessary to establish multidisciplinary interven-
tions. Systematically examining the individual case strengthens the over-
all treatment modalities and can ultimately have a positive impact on the
treatment outcomes.
References:
1. Enright & Sherrill: Am J Respir Crit Care Med 1998
2. Steiber: PLoS One 2016
3. Norman et al: Am J Clin Nutr 2010
4. Stern: Occup Med (Lond) 2014
5. DRKS-ID: DRKS00014263
Disclosure Statement: e authors have nothing to disclose.
552
Application of CDK4/6 Inhibitors in Premenopausal Women
with Hormone Receptor-Positive, HER2-Negative Metastatic
Breast Cancer: a Real-World Experience
Christian M. Kurbacher 1; Lotta Ada Fischer 2; Georg Heinrich 3;
Susanne Herz 1; Alexander Schott 1; A. Tabea Kurbacher 1;
Jutta Anna Kurbacher 4; Christian Rudlowski 5; Mathias R. Warm 2
1Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie I (Schwerpunkt:
Gynäkologische Onkologie), Bonn
2Brustzentrum , Städtisches Klinikum Holweide, Köln
3Praxis für Gynäkologische Onkologie, Fürstenwalde
4Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie II (Allgemeine
Gynäkologie und Geburtshilfe), Bonn
5Frauenklinik, Evangelisches Krankenhaus Bergisch-Gladbach, Bergisch-
Gladbach
Purpose: Recently, a CDK4/6 inhibitor (CDK4/6i) combined with hor-
monal treatment (HTx) is regarded the most eective rst-line therapy
in premenopausal patients (pts) with hormone receptor-positive (HR+),
HER2-negative (HER-) metastatic breast cancer (MBC). is real-world
compilation of data on HTx combined with a CDK4/6i sought to more ac-
curately estimate the importance of this treatment in the clinical routine..
Methods: A total of 33 premenopausal pts were included. Pts were treated
with a CDK4/6i and HTx consisting of ovarian suppression and an aro-
matase inhibitor (AI) in 23 and fulvestrant in another 10 pts; 23 pts re-
ceived palbociclib and 10 pts were given ribociclib for CDK4/6 inhibition.
11 pts had bone only metastases, 7 pts had visceral metastases and 15 pts
suered from mixed metastatic MBC. 15 pts had received prior systemic
therapy for MBC, comprising Ctx in 5, HTx in 7, and both in 3 pts..
Results: 16 pts (48.5%) are still on treatment with a CDK4/6i+HTx. In
the remainder, therapy was terminated due to disease progression. ere
were no additional signals observed indicating signicant bone marrow,
cardiac, liver, or any other serious toxicity. Median treatment duration is
recently 69.4 weeks. Only 3 pts (13.0%) out of this series have died so far
aer 57.1, 109.7, and 140.6 weeks aer starting CDK4/6i so that the me-
dian overall survival is not yet reached. e 2-year survival proportion is
94.4%, the 3-year survival is 56.0%..
Conclusions: ese data show that CDK4/6i+HTx administered to pre-
menopausal pts with HR+, HER2- MBC is safe and eective in the clinical
routine in both the rst and later line setting and conrm results of the
pivotal randomized clinical trials.
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2018
575
Care Appropriate to the Needs of Breast Cancer Patients
with Disability – Results of the CANDY-study
Hannah Gröber 1; Anke Groß-Kunkel 2; Holger Pfa 3;
Euphrosyne Gouzoulis-Mayfrank 1; Ute-Susann Albert 4, 5;
Jürgen Zielasek 1; Sophie E. Groß 1
1LVR-Institut für Versorgungsforschung, LVR-Klinik Köln, Köln, Deutschland
2Humanwissenschaftliche Fakultät, Lehrstuhl Pädagogik und Didaktik bei
Menschen mit geistiger Behinderung, Universität zu Köln, Köln, Deutschland
3Institut für Medizinsoziologie, Versorgungsforschung und
Rehabilitationswissenschaft, Humanwissenschaftliche Fakultät und
Medizinische Fakultät, Universität zu Köln, Köln, Deutschland
4Leiterin des Bereichs Senologie und konservative Gynäkoonkologie,
Frauenklinik. Klinikum Kassel , Kassel, Deutschland
5AWMF-Institut für Medizinisches Wissensmanagement, Philipps Universität,
Marburg, Deutschland
Purpose: As life expectancy is increasing in both the general population
and in people with disabilities, the WHO expects a signicant increase in
cancer diseases among people with and without disabilities over the next
decades. Nevertheless, the needs of people with severe, life-threatening
diseases such as cancer and preexisting disabilities are rarely the focus
of health services research. In order to contribute to a need-based health
care for breast cancer patients with disabilities, the CANDY-study aims to
identify barriers and resources, communication diculties and informa-
tion needs of breast cancer patients with disabilities.
Methods: Within the framework of a DFG-funded study (German Re-
search Foundation) (CAre Appropriate to the Needs of breast cancer pa-
tients with DisabilitY) we will conduct 30 interviews with breast cancer
patients with a severely disabled persons identity card since July 2019.
e patients are recruited in the context of a patient survey for the qual-
ity assurance of breast centers in North Rhine-Westphalia, conducted by
the University of Cologne. e recruitment of breast cancer patients with
various disabilities (physical or sensory impairments, mental illness and
intellectual disability) is performed by means of purposeful sampling. e
interviews are analyzed by content analysis using an inductive and deduc-
tive approach.
Results: So far, there have been 31 positive responses from potential par-
ticipants and the rst interviews have been conducted. e qualitative
analyses of all interviews will be completed by the time of the 34th German
Cancer congress 2020.
Conclusions: Our research aims to clarify the dierent perspectives re-
garding breast cancer care of patients with dierent types of disability.
e CANDY-study will contribute to a more patient-centered provision
of health care for people with disabilities.
Disclosure Statement: none
583
Lung Cancer attributed Mortality among 316,336 Early
Stage Breast Cancer Patients Treated by Radiotherapy or
Chemotherapy, 2000-2015: Evidence from US Cancer Registry
Semaw Abera 1; Rafael Mikolajczyk 2; Eva Johanna Kantelhardt 3;
Christian Ostheimer 4; Dirk Vordermark 4; Daniel Medenwald 1
1Department of Radiation Oncology, Faculty of Medicine and Institute of
Medical Epidemiology, Biostatistics and Informatics (IMEBI), Martin-Luther-
Universität Halle-Wittenberg , Halle (Saale), Deutschland
2 Institute of Medical Epidemiology, Biostatistics and Informatics (IMEBI), Martin-
Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland
3Institute of Medical Epidemiology, Biostatistics and Informatics (IMEBI) and
Department of Gynaecology, Faculty of Medicine, Martin-Luther-Universität
Halle-Wittenberg, Halle (Saale), Deutschland
4Department of Radiation Oncology, Faculty of Medicine , Martin-Luther-
Universität Halle-Wittenberg, Halle (Saale), Deutschland
Purpose: To compare lung cancer attributed mortality among early breast
cancer patients, treated by radio-and/or chemotherapy, relative to the US
female general population. Prognostic factors of lung cancer attributed
mortality were also examined.
Methods: Breast cancer data, covering 2000 to 2015 calendar period,
were extracted from the Surveillance, Epidemiology and End Results-18
(SEER-18) cancer registry database. A comparison of lung cancer attribut-
ed mortality between the breast cancer patients and the general popu-
lation was computed using standardized mortality ratios. Prognostic of
factors of lung cancer mortality and the competing causes were identied
using exible parametric modelling.
Results: Compared with the general population, breast cancer patients
who were treated by radio-and/or chemotherapy, only radiotherapy,
radiochemotherapy and only chemotherapy had 37% (95% CI: 39 - 34%),
34% (95% CI: 37 - 31%), 46% (95% CI: 51 - 40%) and 38% (95% CI: 45 -
31%) lower overall mortality from lung cancer, respectively. Lung cancer
mortality was higher for older patients (compared to those <50 years,
HR50-59=3.29 [95%CI:2.65 – 4.10], HR60-69=7.2 [95%CI: 5.80 – 8.86],
HR70-79=10.46 [95%CI: 8.46 – 12.93], and HR80+=10.39 [95%CI: 8.13 –
13.28]) and for those with negative receptors for estrogen and progestron
hormones (HR=1.37; 95% CI: 1.21 – 1.55). Relative to the married,
patients with widowed, divorced, single or other relationships had 69%,
47% and 25% higher hazard of mortality from lung cancer, respectively.
In contrast, lung cancer mortality was lower for American Indian/Alaska
Native and Aisan/Pacic Islander ethnicities (HR=0.49; 95% CI: 0.39 –
0.62) and for those diagnosed at a recent period (HR2011-2015 vs 2000-2005= 0.79;
95% CI: 0.65 – 0.76).
Conclusions: We found no evidence of higher lung cancer attributed
mortality among the breast cancer patients relative to their background
population. e identied factors could be clinically relevant indicators of
lung cancer attributed mortality aer breast cancer diagnosis.
Disclosure Statement: None
585
Breast Cancer Risk in Familial CHEK2 Germline Mutation
Carriers is Modied by the Polygenic Risk Score: A Multicenter
Study by the German Consortium for Hereditary Breast and
Ovarian Cancer
Julika Borde 1; Corinna Ernst 1; Konstantin Weber-Lassalle 1;
Dieter Niederacher 2; Jan Hauke 1; Judit Horvath 3; Nana Weber-Lassalle 1;
Alfons Meindl 4; Auber Bernd 5; Esther Pohl-Rescigno 1; Norbert Arnold 6;
Andrew Lee 7; Christoph Engel 8; Barbara Wappenschmidt 1;
Marjanka Schmidt 9; Antonis Antoniou 7; Rita Katharina Schmutzler 1;
Karoline Kuchenbaecker 10, 11; Eric Hahnen 1
1Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology
(CIO), University of Cologne, Faculty of Medicine and University Hospital
Cologne, Cologne, Germany
2Department of Gynaecology and Obstetrics, University Hospital Duesseldorf,
Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
3Institute for Human Genetics, University Hospital Muenster, Muenster,
Germany
4Department of Gynecology and Obstetrics, LMU Munich, University Hospital
Munich, Munich, Germany
5Department of Human Genetics, Hannover Medical School, Hannover,
Germany
6Institute of Clinical Molecular Biology, Department of Gynaecology and
Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-
Albrechts University Kiel, Kiel, Germany
7Centre for Cancer Genetic Epidemiology, Department of Public Health and
Primary Care, University of Cambridge, Cambridge, UK
8Institute for Medical Informatics, Statistics and Epidemiology, University of
Leipzig, Leipzig, Germany
9Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The
Netherlands
10Division of Psychiatry, University College London, Maple House, London, UK
11UCL Genetics Institute, University College London, London, UK
Purpose: Pathogenic CHEK2 germline variants associate with a 20-30%
lifetime risk for female breast cancer (BC). It is suggested that additional
genetic factors, such as BC-associated SNPs identied by GWAS, modify
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individual BC risks. For BRCA1/2 mutation carriers, the combined eects
of BC-associated SNPs (polygenic risk score, PRS) have been shown to be
informative for individual risk stratication. e question arises whether
PRS based risk stratication is applicable for CHEK2 germline mutation
carriers with familial BC.
Methods: Here, we analyzed 904 female CHEK2 germline mutation carri-
ers (585 c.1100delC and 208 carriers of other protein-truncating variants,
111 individuals with pathogenic missense variants). A total of 667 muta-
tion carriers were aected by BC (546 unilateral BC, 121 bilateral BC),
with a mean age at rst/secondary diagnosis of 45.9 (23-89)/49.1 (30-79)
years, respectively. 237 mutation carriers were not aected by BC (mean
age at last follow-up: 43.4 (18-92) years). A cohort-approach including
retrospective and prospective events was applied. Multicenter recruitment
was through genetic counseling centers in Germany including index pa-
tients and relatives over a period of 21 years. Genotyping of 77-and 88
established BC-associated SNPs, respectively, was performed using the
Fluidigm® Access Array with subsequent next generation sequencing. A
weighted cohort approach with age at rst BC diagnosis as outcome was
employed to evaluate the association of standardized PRS with BC risk in
CHEK2 mutation carriers.
Results: PRS values computed on the basis of both PRS sets were statisti-
cally signicant associated with BC risk for CHEK2 carriers. e age-spe-
cic hazard ratio estimates were used to compute absolute cumulative BC
risks for mutation carriers by PRS percentiles. CHEK2 carriers at the 10th
percentile of the PRS had a BC risk of approximately 6% compared to
~18% in the 90th percentile by age 60 years.
Conclusions: Combined genotyping of BC-associated SNPs may improve
personalized risk prediction for CHEK2 mutation carriers.
588
Chemotherapy (CT)-Induced Anaemia in Patients (PTS)
Treated with Dose-Dense Regimen: Results of the
Prospectively Randomised Anaemia Substudy from the
Neoadjuvant Geparocto Study
Hans Tesch 1; Sibylle Loibl 2; Karin Kast 3; Christian Jackisch 4; Volker Möbus 5;
Stefanie Buchen 6; Michael Untch 7; Claus Hanusch 8; Sabine Seiler 2;
Michael Weigel 9; Peter A. Fasching 10; Kerstin Rhiem 11; Jens Huober 12;
Jens-Uwe Blohmer 13; Christine Solbach 14; Carsten Denkert 15;
Valentina Nekljudova 2; Theresa Link 3; Andreas Schneeweiss 16
1Centrum für Hämatologie und Onkologie Bethanien, Frankfurt, Germany,
Frankfurt am Main, Deutschland
2GBG, Neu-Isenburg, Germany
3Universitätsklinikum Dresden, Dresden, Germany, Deutschland
4Sana Klinikum Oenbach, Oenbach, Germany
5Klinikum Frankfurt-Höchst, Frankfurt, Germany
6Asklepios Paulinen Klinik Wiesbaden, Wiesbaden, Germany
7Helios Klinikum Berlin-Buch, Berlin, Germany
8Rotkreuzklinikum, München, München, Germany
9Leopoldina-Krankenhaus, Schweinfurt, Schweinfurt, Germany
10Universitätsklinikum Erlangen, Erlangen, Germany
11Universität Köln, Zentrum familiärer Brust- und Eierstockkrebs, Köln, Germany
12Universitätsklinikum Ulm, Ulm, Germany
13Gynäkologie mit Brustzentrum Charité-Universitätsmedizin, Berlin, Germany
14Universitätsklinikum Frankfurt, Frankfurt, Germany
15Institut für Pathologie UKGM, Universitätsklinikum Marburg, Marburg,
Germany
16Nationales Centrum für Tumorerkrankungen, Heidelberg, Heidelberg,
Germany
Purpose: is substudy compared the use of parenteral (IV) ferric car-
boxymaltose (FCM) with physicians choice (PhCh) anaemia therapy in
breast cancer (BC) pts.
Methods: In GeparOcto trial pts with primary BC were randomized to
receive sequential, intensied, dose-dense epirubicin, paclitaxel, and cy-
clophosphamide (iddEPC) or weekly paclitaxel/liposomal doxorubicin
+/- carboplatin (PM(Cb))1. Pts with anaemia grade≥2 (haemoglobin
(Hb)<10g/dl), transferrin saturation (TSAT)≤20% and serum ferrit-
in<300ng/ml (amended to <600ng/ml) were randomized to receive week-
ly FCM or PhCh (no treatment, oral iron, erythropoiesis-stimulating
agent, or both) anaemia therapy. Stratication factors were CT arm (iddE-
PC vs PM(Cb)) and planned PhCh. Primary objective compared the rate
of pts achieving Hb≥11g/dl at 6 weeks (wks) of therapy between two arms.
Main secondary objectives were median time to achieve Hb≥11g/dl and
changes in iron parameters at baseline vs dierent time points.
Results: Less than anticipated pts had CT-induced anaemia. 125 pts were
randomized (62 in FCM, 63 in PhCh). Median age was 46 years (range 26-
66); median levels of Hb, serum ferritin and TSAT were 9.6 (7.6-11.8)g/
dl, 201 (3.0-551)ng/ml and 14.0% (4.0%-76.0%), respectively. Overall, 40
(32.0%) pts (22 in FCM and 18 in PhCh arm; p=0.447) reached Hb≥11g/
dl at 6 wks. Median time to achieve Hb≥11g/dl was 9.0 wks with FCM vs
10.6 wks by PhCh. Median Hb changes vs baseline were comparable in
both arms, while median serum ferritin and TSAT changes at earlier time
points were increased in FCM compared to PhCh.
Conclusions: is is the rst study investigating IV iron treatment for
dose-dense CT-induced anaemia in BC. 32% of pts reached Hb≥11g/dl at
6 wks, irrespective of anaemia therapy. FCM treatment increased ferritin
and TSAT levels but did not improve anaemia in comparison to PhCh in
this setting.
Reference:
1. Schneeweiss et al. Eur J Cancer 2019
Disclosure Statement: e anaemia supportive treatment substudy was nancially
supported by Vifor Pharma Ltd and the GeparOcto trial by Amgen, Roche and
Teva.
HT reported personal fees from Vofor, Roche, Amgen. CH reported personal fees
from Roche, Pzer Novartis, Celgene, Lilly, AstraZeneca outside the submitted
work. SL reported grant from Roche during the work and grants from Celgene,
Novartis, Pzer, Roche, Seattle Genetics, Teva, Vifor, PRIME, Daiichi Sankyo
outside of the submitted work, and patent EP14153692.0. CD reported stock
and other ownership interests from Sividon Diagnostics; honoraria from Teva,
Novartis, Pzer, Amgen; consulting or advisory role from MSD Oncology, Amgen,
Daiichi Sankyo and patents for VMScope digital pathology soware; patent appli-
cation EP18209672 - cancer immunotherapy; patent application EP20150702464
- therapy response. JH reported honoraria, consultancy or advisory role from Lilly,
Novartis, Roche, Pzer, Hexal, Astra Zeneca, MSD, Celgene, Abbvie; grants from
Novartis, Celgene and travel expenses from Roche, Pzer, Novartis, Celgene, Lilly.
AS reported grants from Celgene, Roche, AbbVie, Molecular Partner, personal fees
from Roche, AstraZeneca, Celgene, Pzer, AstraZeneca, Novartis, MSD, Tesaro,
Lilly outside the submitted work. PAF reported grants from Novartis, Biontech,
Novartis, Roche, Pzer, Celgene, Daiichi-Sankyo, Teva, Astra Zeneca, Merck
Sharp & Dohme, Myelo erapeutics, Macrogenics, Eisai, Puma and grants from
Cepheid, during the conduct of the study. VM reported personal fees from Amgen,
Celgene, Roche, Myelotherapeutics, Astra Zeneca, outside the submitted work.
KR reported personal fees from Tesaro, Astra Zeneca, Pzer outside the submitted
work. SS reported grants from Vifor; other from Amgen, Roche, Teva during the
conduct of the study; personal fees Amgen, Hexal, Roche, Mundipharma and oth-
er from Novartis outside the submitted work. TL reported non-nancial support
from AstraZeneca, Pzer, Pharma Mar, Daiichi Sankyo, Roche; personal fees from
MSD, Novartis, Teva, Tesaro. e other co-authors had nothing to disclose.
628
Analysis of ESR1 Mutations in Single Circulating Tumor
Cells from Metastatic Luminal Breast Cancer Patients Upon
Estrogen Deprivation Therapy
André Franken 1; Ellen Honisch 1; Florian Reinhardt 1;
Franziska Meier-Stiegen 1; Liwen Yang 1; Barbara Alberter 2;
Bernhard Polzer 2; Dieter Niederacher 1; Tanja Fehm 1; Hans Neubauer 1
1Department of Obstetrics and Gynecology, University Hospital and Medical
Faculty of the Heinrich-Heine University Duesseldorf, Düsseldorf, Deutschland
2Division “Personalized Tumor Therapy”, Fraunhofer Institute for Toxicology and
Experimental Medicine, Regensburg, Deutschland
Purpose: Mutations in the ligand-binding domain of the ESR1 gene are
frequently observed as a resistance mechanism against estrogen depriva-
tion therapy (EDT) such as aromatase inhibition in breast cancer patients.
Detection of such mutations oers the chance to optimize therapy strate-
gies. However, the predictive utility of the primary tumor for an acquired
resistance is limited and obtaining serial biopsies of metastatic lesions is
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challenging. To underline the application of a liquid biopsy, single circu-
lating tumor cells (CTCs) were analyzed with a next generation sequenc-
ing approach for the ESR1 coding region.
Methods: 132 CTCs from blood samples of 46 metastatic breast cancer
patients were analyzed. CTCs were enriched with the CellSearch® system,
isolated and genomic DNA was amplied. Furthermore, tumor tissue
samples from corresponding primary tumors and/or metastatic lesions
from patients with ESR1 mutations in CTCs were analyzed.
Results: ESR1 mutations were detected in CTCs from twelve of 46 pa-
tients exclusively in the patient group that was treated with EDT. No ESR1
mutations were found in CTCs from patients who received no or other ET
(p-value: 0.048). In seven patients mutations were detected in the hotspot
regions located in the ligand binding domain. Six novel mutations were
detected. ESR1 mutations were absent in primary tumor tissue samples of
patients with mutated CTCs.
Conclusions: Single cell CTC analysis for ESR1 mutations may be of clin-
ical value to identify patients who might progress under EDT and might
therefore benet from an early switch to an alternative ET or other treat-
ment regime.
636
Germline (G)BRCA1/2 Mutations (M) and Hematological
Toxicities in Patients (PTS) with Triple Negative Breast Cancer
(TNBC) Treated with Neoadjuvant Chemotherapy (NACT)
Jenny Furlanetto 1; Volker Möbus 2; Andreas Schneeweiss 3; Kerstin Rhiem 4;
Hans Tesch 5; Jens-Uwe Blohmer 6; Kristina Lübbe 7; Michael Untch 8;
Christoph Salat 9; Jens Huober 10; Peter Klare 11; Rita Schmutzler 4;
Fergus J. Couch 12; Bianca Lederer 1; Bernd Gerber 13; Dirk-Michael Zahm 14;
Ingo Bauerfeind 15; Valentina Nekljudova 1; Claus Hanusch 16;
Christian Jackisch 17; Theresa Link 18; Sibylle Loibl 1; Peter A. Fasching 19
1GBG, Neu-Isenburg, Germany
2Klinikum Frankfurt-Höchst, Frankfurt, Germany
3Nationales Centrum für Tumorerkrankungen, Heidelberg, Heidelberg, Germany
4Zentrum Familiärer Brust- und Eierstockkrebs, Uniklinik Köln, Köln, Germany
5Centrum für Hämatologie und Onkologie Bethanien Frankfurt, Frankfurt
Germany
6Brustzentrum Charité-Universitätsmedizin Berlin, Berlin, Germany
7DIAKOVERE Henriettenstift, Klinik für Gynäkologische Chirurgie, Senologie und
Onkologie, Hannover, Hannover, Germany
8HELIOS Klinikum Berlin Buch, Berlin, Germany
9Hämatologisch-Onkologische Schwerpunktpraxis Salat/Stötzer, München,
München, Germany
10Universitätsfrauenklinik Ulm, Ulm, Germany
11MediOnko-Institut GbR Berlin, Berlin, Germany
12Division of Experimental Pathology and Laboratory Medicine, Department of
Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
13Universitätsfrauenklinik am Klinikum Südstadt, Rostock, Rostock, Germany
14SRH Wald-Klinikum Gera, Gera, Germany
15Klinikum Landshut, Landshut, Germany
16Rotkreuzklinikum, München, München, Germany
17Sana-Klinikum, Oenbach, Oenbach, Germany
18Universitätsklinikum Dresden, Dersden, Germany
19University Hospital Erlangen, Erlangen, Germany
Purpose: BRCA1/2 plays a central role in DNA repair. Pts with gBRCA1/2m
treated with CT might be at higher risk of acute hematological toxicities
(hemtox) due to the lower level of functional BRCA1/2 protein. Published
results are discordant.
Methods: Pts with early TNBC and known gBRCA1/2m treated with an-
thracycline-taxane based NACT in the GeparQuinto (n=487), GeparSixto
(n=291) and GeparOcto (n=393) studies were included. Primary G-CSF
prophylaxis was foreseen only under iddETC in GeparOcto. Primary ob-
jective: rate of neutropenia grade (G)3-4 aer cycle 1 (C1); secondary ob-
jectives: rate of other hemtox G3-4, overall rate aer C1 and under taxane.
Results: 209/1171 pts (17.8%) had a gBRCA1/2m (177 gBRCA1m, 33
gBRCA2m). Median age was 48yrs [21-78]. e rate of neutropenia
G3-4 aer C1 in gBRCA1/2 wildtype (wt) vs gBRCA1/2m was 35.7% vs
37.4% (OR 1.08, 95%CI 0.78-1.48, p=0.658; multivariate analysis (MVA)
OR 1.26, 95%CI 0.87-1.82, p=0.226). No dierence was found in other
hemtox. gBRCA1/2 m status did also not predict for other hemtox G3-4
(OR 0.94, 95%CI 0.64-1.40, p=0.773; MVA OR 0.94, 95%CI 0.62-1.43,
p=0.779). No dierence was seen according to gBRCA1 or 2 m. Under tax-
ane, the rate of hemtox G3-4 in gBRCA1/2 wt vs gBRCA1/2m was 43.1%
(n=270) vs 59.5% (n=91) (OR 1.94, 95%CI 1.35-2.77, p<0.001; MVA OR
2.91, 95%CI 1.55-5.45, p=0.001); anemia G3-4 2.6% vs 3.3% p=0.584; leu-
copenia G3-4 32.7vs 47.1% p=0.001; neutropenia G3-4 35.8% vs 49.3%
p=0.003; thrombopenia G3-4 1.4% vs 4.6% p=0.024; febrile neutropenia
5.9% vs 4.6% p=0.696.
Discussion: We show that gBRCA1/2m are not associated with a signi-
cantly higher risk of severe hemtox. Under taxane, pts with gBRCA1/2m
demonstrate a higher rate of hemtox G3-4, especially neutropenia, com-
pared to wt pts.
Conclusions: Pts with gBRCA1/2m receiving taxane therapy should be
carefully monitored, being at higher risk for severe hemtox.
Disclosure Statement:
V. Möbus: AMGEN, Roche, Celgene, Myelotherapeutics, Astra Zeneca.
A. Schneeweiss: Celgene, Roche, AbbVie, Molecular Partner, Novartis,
AstraZeneca, MSD, Tesaro, Pzer, Lilly.
H. Tesch: Roche, Novartis.
K. Lübbe: Roche, Novartis, Genomic Health, Lilly.
M. Untch: Lilly Int., MSD Merck, Mundipharma, Myriad Genetics, Odonate,
Pzer GmbH, PUMA Biotechnology, Roche Pharma AG, Sano Aventis
Deutschland GmbH, TEVA Pharmaceuticals Ind Ltd, Novartis, Abbvie, Amgen
GmbH, Astra Zeneca, BMS, Celgene GmbH, Daiji Sankyo, Eisai GmbH, Lilly
Deutschland.
J. Huober: Novartis, Lilly, Roche, Pzer, Astra Zeneca, MSD, Celgene. C; A;
Lilly, Novartis, Roche, Pzer, Hexal, Astra Zeneca, MSD, Celgene. C; A; Celgene,
Novartis. O; A; Roche, Pzer, Novartis, Celgene, Daichi.
F.J. Couch: Qiagen, Ambry Genetics. O; A; AstraZeneca, GRAIL.
I. Bauerfeind: CELGENE, Roche.
C. Hanusch: Roche, Novartis, Lilly Pharma, Celgene, Astra Zeneca.
C. Jackisch: Roche, Amgen.
T. Link: Amgen, AstraZeneca, Pzer, Pharma Mar, Daiichi Sankyo, MSD,
Novartis, Teva, Tesaro, Roche.
S. Loibl: Patent EP14153692.0 pending. Roche, AbbVie, Amgen, AstraZeneca,
Celgene, Novartis,
Pzer, Roche, Seattle Genetics, Teva, Vifor, PRIME, Daiichi.
P.A. Fasching: Novartis, Biontech, Roche, Pzer, Celgene, Daiichi-Sankyo, TEVA,
Astra Zeneca, Merck Sharp & Dohme, Myelo erapeutics, Macrogenics, Eisai,
Puma, Cepheid.
e other co-authors had nothing to disclose.
657
Impact of Marging Shaving on Re-Excision Rates in Patients
with Primary Invasive Carcinoma and Carcinoma in Situ
InBreast Conserving Surgery. Data from a Population Based
Cohort of Clinical Cancer Registry
Miriam Fernandez-Pacheco 1; Ec Inwald 1; Michael Gerken 2;
Atanas Ignatov 1; Monika Klinkhammer-Schalke 2; Olaf Ortmann 1
1University Medical Center Regensburg. , Department of Gynaecology and
Obstetrics. , Regensburg, Deutschland
2Institute for Quality Management and Health Services Research, Tumor Center,
University of Regensburg , Regensburg, Deutschland
Purpose: Previous studies reported considerably high re‐excision rates
in breast‐conserving surgery (BCS) about 20%. Circumferencial Marging
Shaving (CMS) could be a surgical strategy to reduce re‐excision rates.
is study aimed to investigate the eects of CMS during BCS on reducing
residual tumor.
Methods: Totally, 440 patients with primary carcinoma or carcinoma in
situ of the breast who underwent BCS in the University Medical Center
Regensburg between 2017 and 2019 were analyzed. Patients who had CMS
or targeted re‐excision (TRE) depending on intraoperative mammogra-
phy or sonography were compared with patients receiving BCS without
removal of further tissue during primary surgery. e impact of these sur-
gical methods on residual tumor (R1) and further necessary intervention
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was analyzed by means of multivariable binary logistic regression model
adjusting for tumor size, nodal status, histologic al type, tumor biology,
neoadjuvant chemotherapy, surgeon, breast side, and patient´s age.
Results: A total of 306 patients had invasive‐ductal carcinoma. Of these,
40 patients received CMS, 82 TRE, and 184 no further excision. Aer
comparing these subgroups in a binary regression model there was a
tendency for CMS and TRE to have advantage over missing re‐excision
regarding residual tumor. Furthermore, aer adjusting for dierent vari-
ables, especially patients with T1‐tumors had a slightly signicant benet
from CMS.
Conclusions: Our results indicate a tendency that CMS reduces residual
tumor compared to TRE or to no further surgical action, although nal
results will be presented.
References:
1. Eect of cavity margin shavings to ensure completeness of excision on local re-
currence rates following breast conserving surgery. Barthelmes, L et al. Europ.
Journ. of Surg. Oncol., Vol. 29, Issue 8, 644 - 648
2. Systematic cavity shaving: Modications of breast cancer management and
long-term local recurrence, a multicentre study. Héquet, D. et al., Europ. Journ.
of Surg. Oncol., Vol. 39, Issue 8, 899 - 905
Disclosure Statement: e authors declare no conict of interest.
667
Pro and Contra Conversation: Vitamin D Deciency
and Cancer: Fact or Fiction?
André Robert Rotmann
Prof. Dr. Ingo Diel, Praxisklinik am Rosengarten, Mannheim, Deutschland
Vitamin D deciency and cancer Fact or ction?
It is undisputed that vitamin D is one of the central hormones of our body.
Likewise, vitamin D is needed to provide minerals like calcium for your
metabolism
making it indispensable for bone health.
Numerous studies show that vitamin D deciency is responsible for an
increased risk of developing common diseases such as diabetes, cardio-
vascular diseases, or even depression.
In addition, a link with the immune system and the development of can-
cer is postulated.
A current PUBMED search using the terms “vitamin D” and “cancer” re-
sulted in more than 10,000 hits!
e complementary and integrative oncologists are also increasingly con-
cerned with the possible consequences of vitamin D deciency and, ac-
cordingly, with substitution.
2 experts who deal with osteo-oncology will look at this exciting topic
with a pro and con discussion.
Prof. Ingo Diel from Mannheim is a proven, nationally and internationally
well-known osteo-oncologist and will take the contra position.
Dr. Andre Rotmann from Rodgau, gynaecologist-oncologist and actively
involved for years in the integrative and complementary medical treat-
ment of gynaecological tumours will take the pro position.
e discussion should be conducted based on the current status of science
and represent exciting and entertaining aspects of this current topic.
674
Breaking News from the Field of Complementary Oncology,
an Exiting Presentation of New Integrative Therapies in Breast
Cancer Patients
André Robert Rotmann
Rodgau, Rodgau, Deutschland
e aims of the integrative and complementary oncology is to minimalize
the side eects of the classic oncologic therapy including such as chemo-
therapy or antiendocrine therapy and above all to enhance life quality of
patients
ere is a great interest among patients worldwide in complementary on-
cological approaches.
e prognosis in the metastasing stage is unfortunately still poor
Curcumin is a plant-based substance known for thousands of years that is
seen as a promising substance in numerous preclinical studies, studies of
carcinoma cell lines and in animal research.
It has been reported to have a synergistic eect with a number of chemo-
therapeutic substances.
e aim of our randomised, double-blind, placebo-controlled study was
to demonstrate the ecacy of curcumin in combination with taxane in the
treatment of advanced breast cancer for the rst time
“Study of Ecacy of Curcumin in Combination with Chemotherapy in
Patients with advanced Breast Cancer: Randomized, Double Blind, Place-
bo Controlled Clinical Trial.
150 patients with advanced breast cancer were randomly divided into two
groups of 75 each.
Group A were given paclitaxel with an intravenous placebo for a total of
12 weeks
Group B received curcumin 300 mg intravenously + paclitaxel q1w also
for 12 weeks
e aim of the study was to demonstrate the potential benets of curcum-
in administered intravenously in combination with paclitaxel compared
with the placebo and paclitaxel for patients with advanced breast cancer
e primary objectives were the ecacy of the combined treatment with
regard to the objective response rate (ORR), progression-free survival
(PFS), time-to-tumour progression (TTP), quality of life (QoL) as well as
the inuence of tumour markers
e secondary objectives were treatment safety and the observation of
possible side eects and disease progression
e exact design of the study and the dierentiated results were presented
and discussed for the rst time anywhere in the world at the 2019 German
Senology Congress in Berlin. is lecture was awarded high-ranking and
will be published soon
683
Cancer Management and Outcome of Young Patients (PTS)
with Breast Cancer (BC) Diagnosed at 40 Years (YRS) or
Younger
Sabine Seiler 1; Sabine Schmatloch 2; Mattea Reinisch 3; Tanja Neunhöer 4;
Marcus Schmidt 5; Christina Bechtner 6; Frederik Marmé 7;
Michael Wagner 8; Volker Möbus 9; Toralf Reimer 10; Anke Kleine-Tebbe 11;
Bruno Sinn 12; Elmar Stickeler 13; Michael Untch 14; Wolfgang Janni 15;
Fenja Seither 1; Sibylle Loibl 1
1GBG, Neu-Isenburg, Germany
2Brustzentrum, Elisabeth Krankenhaus Kassel, Kassel, Germany
3Brustzentrum, Kliniken Essen-Mitte, Essen, Germany
4Helios Dr. Horst Schmidt Kliniken, Wiesbaden, Wiesbaden, Germany
5Universitätsmedizin Mainz, Mainz, Germany
6Brustzentrum, Klinikum Memmingen, Memmingen, Germany
7Universitätsfrauenklinik Mannheim, Mannheim, Germany
8Siloah St. Trudpert Klinikum, Pforzheim, Pforzheim, Germany
9Klinik für Gynäkologie und Geburtshilfe, Klinikum Frankfurt Höchst, Frankfurt,
Germany
10Universitätsfrauenklinik und Poliklinik am Klinikum Südstadt Rostock, Rostock,
Germany
11Brustzentrum, DRK Kliniken Berlin, Berlin, Germany
12Institut für Pathologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
13Uniklinik RWTH Aachen, Aachen, Germany
14HELIOS Klinikum Berlin Buch, Berlin, Germany
15Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
Purpose: To provide data about modern BC treatment and oncological
outcome of young women aged ≤40 yrs.
Methods: e BC in pregnancy registry (BCP/GBG29) is a multicenter,
observational study that compares the management and outcome of BC
in pregnancy with non-pregnant pts ≤40 yrs as control cohort. All pts are
treated according to local standards. is analysis reports descriptively
baseline characteristics, BC therapy, short-term and long-term outcome
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of the young control cohort. Disease-free (DFS) and overall survival (OS)
rates were estimated using the Kaplan-Meier method.
Results: 964 non-pregnant women with a median follow-up of 38.7
months (95%CI 35.2-41.3) comprised the analysis set. Median age was 35
yrs (range 19-40). At diagnosis, 90.4% of pts had a stage T1-2 and 67.0%
were nodal negative; 42.7% had HR+/HER2- BC, 31.9% HER2+ BC and
25.4% triple-negative BC (TNBC). 3.2% of pts were M1 at primary di-
agnosis. 90.7% of pts with early BC (EBC) received chemotherapy (CT).
93.4% of pts with endocrine treatment for EBC received tamoxifen; there-
of 35.8 % with a GnRH analogue. Regardless of BC subtype, the high-
est pCR rates (ypT0 ypN0) were achieved in the cohort of pts age 18-29
yrs (HER2+ 47.8%, TNBC 65.2%, HR+/HER2-40.0%). e 3-yr DFS for
pts with EBC was 83.1% (95%CI 79.6%-86.0%) and the 3-yr OS 94.3%
(95%CI 91.9%-96.0%). e subgroup analysis per BC subtype suggested
a trend towards inferior DFS only in the group of pts ≤34 yrs and HR+/
HER2−BC (log rank p=0.058). 3.4% of pts got pregnant aer BC with a
median time from diagnosis to birth/termination of 3 yrs (range 2-7).
Conclusions: In this large cohort of young BC pts the reported treatments
reect the modern oncological management of these pts. e prognostic
relevance of young age by itself could not be shown for pts with HER2+
and TNBC. Yet, similar to previously reported results1 our data suggest a
trend towards inferior DFS in the group of pts ≤34 yrs and HR+/HER2−
BC.
Reference:
1. Loibl S, et al. Breast Cancer Res Treat. 2015
Disclosure Statement: SL reported grant from Roche during the work and grants
from Celgene, Novartis, Pzer, Roche, Seattle Genetics, Teva, Vifor, PRIME,
Daiichi Sankyo outside of the submitted work, and patent EP14153692.0. SS
reported consulting fees from Roche, Amgen, Novartis, Hexal. MR reported
personal fees and non-nancial support from Novartis , personal fees from Roche
, non-nancial support from Celgene , personal fees from Lilly , personal fees
from Astra Zeneca , personal fees and non-nancial support from Pzer, outside
the submitted work; MS reported grants and personal fees from Pierre-Fabre,
grants, personal fees and non-nancial support from Roche, grants, personal fees
and non-nancial support from Pzer, grants and personal fees from Novartis,
grants and personal fees from Astra-Zeneca, grants and personal fees from Eisai,
personal fees from Amgen, personal fees from Celgene, grants, personal fees and
non-nancial support from Pantarhei, grants and non-nancial support from
BioNTech, grants from Genentech, outside the submitted work; In addition, MS
has a patent EP2469440 (A3) Molecular markers for cancer prognosis pending,
a patent WO2009033941 (A1) A method for predicting the response of a tumor
in a patient suering from or at risk of developing recurrent gynecological cancer
towards a chemotherapeutic agent pending, and a patent WO2014118333 (A1)
Method for predicting the benet from inclusion a taxane in a chemotherapy
regimen in patients with breast cancer pending. FM reported personal fees and
non-nancial support from AstraZeneca, personal fees from Clovis, personal fees
from Tesaro, personal fees and non-nancial support from Roche, personal fees
and non-nancial support from Novartis, personal fees from AMGEN, personal
fees and non-nancial support from Pzer, personal fees from Curevac, personal
fees from Vaccibody, personal fees from PharmaMar, personal fees from Eisai,
personal fees from Celgene, personal fees from GenomicHealth, outside the sub-
mitted work; ES reported Travel Sponsoring from Roche and consulting fees from
Roche, Novartis, Pzer, Astra Zeneca. VM reported consulting fees from Amgen,
Roche, Tesaro, AstraZeneca and personal fees for advisory board from Amgen,
Roche, Myeloerapeutics.
e other co-authors had nothing to disclose.
694
A Randomized, Double-Blind, Phase III Trial of Neoadjuvant
Chemotherapy (NACT) with atezolizumab/Placebo in
Patients with Triple-Negative Breast Cancer (TNBC) Followed
by Adjuvant Continuation of atezolizumab/Placebo
(Gepardouze)
Sibylle Loibl 1; Christian Jackisch 2; Sabine Seiler 1; Priya Rastogi 3;
Jens Huober 4; Carsten Denkert 5; Andreas Schneeweiss 6; Claus Hanusch 7;
Peter A. Fasching 8; Jens-Uwe Blohmer 9; Michael Untch 10; Kerstin Rhiem 11;
Christine Solbach 12; Valentina Nekljudova 1; Joseph Costantino 3;
Norman Wolmark 13; Charles Geyer 14
1GBG, Neu-Isenburg, Germany
2Sana Klinikum Oenbach, Oenbach, Germany
3National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh,
University of Pittsburgh Cancer Institute School of Medicine, Pittsburg, USA
4Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm,
Germany
5Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum
Marburg, Marburg, Germany
6Nationales Centrum für Tumorerkrankungen, Heidelberg, Heidelberg, Germany
7Rotkreuzklinikum, München, München, Germany
8Universitätsklinikum Erlangen, Erlangen, Germany
9Gynäkologie mit Brustzentrum Charité-Universitätsmedizin, Berlin, Germany
10Helios Klinikum Berlin-Buch, Berlin, Germany
11Universität Köln, Zentrum familiärer Brust- und Eierstockkrebs, Köln, Germany
12Universitätsklinikum Frankfurt am Main, Frankfurt, Germany
13National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, UF
Health Cancer Center at Orland Health, Orlando, USA
14National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh,
Virginia Commonwealth University, Massey Cancer Center in Richmond,
Richmond, USA
Purpose: TNBC is associated with higher percentages of pathological
complete response (pCR) to NACT, and patients (pts) with a pCR have
a favorable prognosis. Pts with residual disease have a substantially
higher risk of recurrence than pts with other subtypes of breast cancer.1,2
erapeutic blockade of PD-L1 binding by atezolizumab has resulted in
relevant anti-tumor ecacy.3,4 e aim of GeparDouze is to determine
whether the addition of atezolizumab to NACT and adjuvant therapy
improves pCR and event free survival (EFS) in pts with TNBC.
Methods: GeparDouze (NSABP B-59/GBG96) is a phase III, double
blind, placebo-controlled trial. 1520 pts will be randomized (1:1) to
NACT + atezolizumab 1200mg or placebo IV every 3wks followed by ad-
juvant atezolizumab 1200mg or placebo IV for 6 months. Stratication
factors are Group (NSABP Foundation Inc.; GBG), tumor size (1.1-3.0cm;
>3.0cm), epirubicin or doxorubicin/cyclophosphamide schedule (q2w;
q3w), nodal status (positive; negative) and PD-L1 Status (positive; nega-
tive; indeterminate). Pts with primary cT1c-cT3 TNBC and centrally as-
sessed hormone receptor-status, HER2-status, and PD-L1-status on core
biopsy can be enrolled. Co-primary endpoints are pCR (ypT0/Tis ypN0)
and EFS. Main secondary endpoints are overall survival, recurrence-free
interval, distant disease-free survival, and toxicity.
Results: GeparDouze is an academic collaboration between NSABP and
GBG. So far, 357 patients are enrolled. It is expected that approximately
760 pts will be randomized within 34 months by NSABP sites and approx-
imately 760 patients by GBG sites.
Conclusions: GeparDouze will provide further data on ecacy and safety
of atezolizumab in pts with TNBC.
References:
1. Liedke C. J Clin Oncol. 2008.
2. Hahnen E. JAMA Oncol.2017.
3. Adams S. J Clin Oncol. 2016.
4. Schmid P. Cancer Res. 2017.
Disclosure Statement: e trial is nancially supported by Genentech/Roche.
SL reported grant from Roche during the work and grants from Pzer, Celgene,
Amgen, Novartis, AstraZeneca, Abbvie, Lilly, Daiichi Sankyo, Eirgenix outside of
the submitted work, and patent pending EP14153692.0. JC reported grants from
Genentech. CJ reported personal fees from Roche, Celgene during the conduct
of the study. CG reported grants from Genentech/Roche during the conduct of
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2018
the study; grants and non-nancial support from AstraZeneca, Abbvie, Genen-
tech/Roche; personal fees from Celgene outside the submitted work. SS reported
grants from Genentech/Roche during the conduct of the study. NW reported
other from Genentech/Roche during the conduct of the study. PR reported grants
from Genentech/Roche during the conduct of the study; other from AstraZeneca,
Genentech/Roche, Lilly outside the submitted work. CD reported shareholder
and cofounder from Sividon Diagnostics; honoraria/consultation from Teva,
Novartis, Pzer, Roche, Amgen, MSD, Daiichi Sankyo, Celgene, AstraZeneca;
atent application: EP18209672 – cancer immunotherapy. MU reported fee to the
institution from BMS, Lilly, PUMA Biotechnology; fee and non-nancial support
to the institution from Abbvie, Amgen, AstraZeneca, Celgene, Daiji Sankyo, Eisai
GmbH, Janssen Cilag, Johnsen&Johnsen, MSD Merck, Lilly, Mundipharma, Myri-
ad Genetics, Odonate, Pzer, Riemser, Roche, Sano Aventis Deutschland GmbH,
Sividon Diagnostics, TEVA Pharmaceuticals Ind Ltd outside the submitted work.
AS reported grants from Celgene, Roche, AbbVie, Molecular Partner, personal fees
from Roche, AstraZeneca Celgene, Roche, Celgene, Pzer, Novartis, MSD, Tesaro,
Lilly outside the submitted work. e other co-authors had nothing to disclose.
748
Predicting the Risk of Locoregional Recurrence after
Early Breast Cancer: an External Validation of the Dutch
Inuence-Nomogram with Clinical Cancer Registry Data
from Germany
Teresa Draeger 1, 2; Vinzenz Völkel 1, 2; Michael Gerken 2;
Monika Klinkhammer-Schalke 2; Sabine Siesling 3
1Caritas Krankenhaus St. Josef, Regensburg, Deutschland
2Tumorzentrum Regensburg, Regensburg, Deutschland
3Universität Twente, HTSR, Enschede, Niederlande
Purpose: Regular follow-up aer breast cancer treatment aims for ear-
ly detection of locoregional recurrences (LRR) to improve the patients
outcome. By estimating individual 5-year recurrence-risks based on dif-
ferent patient- tumor- and treatment characteristics, the Dutch INFLU-
ENCE-nomogram can assist health professionals and patients in devel-
oping personalized risk-based follow-up pathways. e objective of this
study is to externally validate the INFLUENCE-nomogram on non-Dutch
patients.
Methods: Data derive from a large clinical cancer registry in southern
Germany, covering a population of 1.1 million. 6520 Patients with curative
resection of early-stage breast cancer, diagnosed between 2000 and 2012,
were included in the analysis. For every included patient, an individual
LRR-risk was estimated by the INFLUENCE-nomogram. Its predictive
ability was tested by comparing estimated and observed LRR-probabilities
using the Hosmer–Lemeshow goodness-of-t test and C-statistic based
on the receiver-operator-characteristic (ROC) curve.
Results: In the German validation-cohort, 2.8% of the patients developed
an LRR within 5 years aer primary surgery (n = 184). While the IN-
FLUENCE-nomogram generally underestimates the actual LRR-risk of
the German patients (p < 0.001), its discriminative ability is comparable
to the one observed in the original Dutch modeling-cohort (C-statistic
German validation-cohort: 0.73, CI 0.69–0.77 vs. C-statistic Dutch mod-
eling-cohort: 0.71, CI 0.69–0.73). Similar results were obtained in most
of the subgroup analyses stratied by age, type of surgery and intrinsic
biological subtypes.
Conclusions: e presented outcomes underline the generalizability of
the recently developed INFLUENCE-nomogram beyond the Dutch pop-
ulation. e model performance of INFLUENCE could be enhanced in
future by incorporating additional risk factors for LRR.
Funding: Funded by the Deutsche Forschungsgemeinscha (DFG, German
Research Foundation) – project number 417891978.
774
Predicting the Eectiveness of Sensor-Controlled Scalp
Cooling to Prevent Chemotherapy-Induced Alopecia in
Primary Breast Cancer Patients: It is the Regimen that Matters
Aila Ritter 2; A. Tabea Kurbacher 2; Susanne Herz 2; Nele Kettelhoit 2;
Gabriele Kolberg 2; Jutta A. Kurbacher 1; Claudia Schweitzer 2;
Christian M. Kurbacher 2
1Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie II (Allgemeine
Gynäkologie und Geburtshilfe), Bonn
2Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie I (Schwerpunkt:
Gynäkologische Onkologie), Bonn
Purpose: Sensor-controlled scalp cooling (SCSC) is now an accepted
means to prevent primary breast cancer (PBC) patients (pts) from chemo-
therapy (Ctx)-induced alopecia (CIA). is retrospective study sought to
determine pts who are most likely to benet from SCSC while being sub-
jected to CIA-inducing neoadjuvant (NACT) or adjuvant chemotherapy
(ACT) with anthracyclines (A), taxanes (T), or both.
Methods: 86 pts were included: NACT, 47 (54.6%); ACT, 39 (45.4%); dose-
dense (dd) Ctx, 38 (44.2%); non-dd Ctx 48 (55.8%); premenopausal, 48
(55.8%); postmenopausal, 38 (44.2%). Ctx regimens: A→T, 38 (44.2%),
T→A, 23 (26.7%), T, 25 (29.1%). CIA was quantied according to the Dean
score (DS). Data were analyzed regarding the SCSC completion rate, and
quality of hair preservation (success: DS 0-2, failure: DS 3-4). Moreover, the
following parameters were investigated in regard to the success of SCSC:
menopausal status, NACT vs ACT, dd Ctx vs non-dd Ctx, Ctx regimen.
Results: e success rate was 64.0% with 35 pts (40.7%) experiencing DS
0, and 20 (23.3%) showing DS 1-2. Eectiveness of SCSC did not dier for
most analyzed subgroups. e relative risk (RR) to experience CIA was 1.23
(CI: 0.87-1.74) for post- vs premenopausal pts, 1.07 (CI: 0.78-1.46) for ACT
vs NACT, 1.28 (CI: 0.91-1.80) for dd Ctx vs non-dd Ctx, and 1.556 (0.98-
2.36) for A+T vs T. However, the SCSC success rate for A→T (47.4%) was
signicantly lower (p = 0.016) as compared to T→A (73.9%) or T (80.0%).
Conclusions: SCSC was eective to prevent CIA in pts with PBC. All
therapeutic subgroups beneted from SCSC. A+T-based Ctx per se is not
a contraindication for SCSC. However, the success rate is signicantly
higher when the taxane precedes the anthracycline.
Disclosure Statement: All authors declare no conict of interests. t
775
The Aesthetic Results for Reconstruction After Oncoplastic
Breast Surgery
Anna Sukhotko; Aziz Zikiryahodjaev; Maria Ermoshenkova;
Artur Tukmakov
Moscow P.A. Gerzens Cancer Research Institute – The National Medical
Research Radiologic Center of the Ministry of Health of the Russian Federation,
Moscow, Russland
Purpose: To create of the new concept of surgical treatment as a compo-
nent of multi-therapy treatment of patients with breast cancers on postop-
erative quality of life (Qol).
Methods: We assessed 437 women who underwent breast conserving sur-
gery (BCS) or total mastectomy (TM) with immediate reconstruction in
P.A. Gertsen Moscow Research Institute from 2013 to 2018. Of the 437
patients, 290 (66,4%) had BCS,147( 33,6%) – skin-sparing mastectomy
(SSM). BCS included glandular reshaping (rotation ap, round-block
technique, batwing mastopexy, wise pattern-inverted T, vertical pattern).
Aer SSM, 7(4,7%) patients underwent immediate breast reconstruction
using a transverse rectum abdominis musculocutaneous (TRAM) ap,
47 (31,9%) - musculotoracodorsal (TDL) ap, 98 (66,7%) - musculolatis-
simus dorsi ap and it combination with endoprosthesis. A median fol-
low-up period was 58 months. Only 94 (21,5%) patients received adjuvant
polychemotherapy, combinations adjuvant polychemotherapy and radia-
tion therapy – 27 (6,1%) or endocrine therapy – 37(8,5%).
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Results: During a median follow-up period local recurrent were detected
at 30 (6,9%), distant metastasis – 65 (14,9%) patients. Overall disease-free
survival in patients with BCS stage I was 96,2%, IIA– 90%, IIB – 86,7%,
IIIA – 86,2% (р>0,05). Overall disease-free survival in patients with SSM
stage I was 92,9%, IIA– 91,2%, IIB – 84,4%, IIIA – 91,4% (р>0,05). e
postoperative cosmetic result aer BCS was assessed in 89,3% patients.
Conclusions: Oncoplastic surgery contributes is the better phychological
adaptation of patients. Variety of modications and options of reconstruc-
tive surgery causes problem of choice, which should be solved with patient
taking into account the clinical data. e extent of surgical intervention
does not aect the performance of the 5-year overall and recurrent surviv-
al and depends on the distribution process.
Reference:
1. Zork NM, et al. e eect of dedicated breast surgeons on the short-term
outcomes in breast cancer. Ann Surg. 2018;248(2):280-5.
Disclosure Statement: I agree
783
Surgical Resection of The Primary Tumor is Associated with
Increased Long-Term Survival in Patients with Stage IV
Breast Cancer
Anna Sukhotko; Aziz Zikiryahodjaev; Larisa Bolotina
Moscow P.A. Gerzens Cancer Research Institute – The National Medical
Research Radiologic Center of the Ministry of Health of the Russian Federation,
Moscow, Russland
Purpose: e problem of the treatment of disseminated breast cancer
(DBC) is specially urgent in the present situation, as there is no uniform
standard of care for these patients nowadays. Treatment of patients with
stage IV breast cancer is palliative, and, in some cases, symptomatic, so the
main task is to maximally prolong the life and improve its quality.
Methods: is investigation comparatively analyzed the results of com-
plex treatment with metastatic breast cancer. We analyzed retrospectively
treatment experience of 196 patients with generalized breast cancer in the
department of oncology and breast reconstructive surgery of P.A. Herzen
Moscow Cancer Research Institute from 2000 to 2018 Invasive ductul car-
cinoma was veried in128 patients (65,3%), invasive lobular carcinoma
- 33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving
drug and radiation therapies was performed in two patient groups. e
rst group includes 124 patients who underwent surgical intervention as
complex treatment, the second group includes 72 patients with only med-
ical therapy. Standard systemic therapy was given to all patients.
Results: Overall, 3-and 5-year survival in st group was 43,8 and 21%,
in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median
survival in patients with surgical treatment composed 32 month, in pa-
tients with only systemic therapy - 21. e factors having inuencing an
inuence on the prognosis and the quality of life outcomes for of patients
with generalized breast cancer were are also studied: hormone-dependent
tumor, Her2/neu hyper-expression, reproductive function status (age,
menopause existence).
Conclusions: Removing primary breast tumor in patients with general-
ized breast cancer improve long-term outcomes. ree- and ve-year sur-
vival increased by 28,7 and 16,3% respectively, and median survival – for
11 months. ese patients may benet from resection of the breast tumor.
One explanation for the eect of this resection is that reducing the tumor
load inuences metastatic growth.
Disclosure Statement: I agree
801
Transcriptional Factor KLF11 (Kruppel Like Factor 11)
As Potential Targets and a New Biomarker for the Prognosis
of Human Breast Cancer
LILI LIN; Kristina Pfender; Anna Hester; Udo Jeschke; Christina Kuhn
LMU Munich, University Hospital., Obsterics and Gynecology, München,
Deutschland
Purpose: is study aims to clarify prognostic impact of KLF11 in breast
cancer.
Methods:
1. We retrieved four independent investigation from ONCOMINE data-
base and investigate the prognostic signicance of KLF11 mRNA level
in patients with BC, by using the Kaplan-Meier Plotter online database.
2. We collected and analyzed the expression of KLF11 in 312 BC samples
by immunohistochemistry in our patients’ cohort and correlated its ex-
pression with several parameters and patient outcome.
Results: According to the meta-analysis across four ONCOMINE
datasets, we revealed KLF11 was one of the mostly down-regulated
genes in BC. Interestingly, also a meta-analysis from Kaplan-Meier
Plotter online database demonstrate that patients with KLF11 high
expression had signicantly shorter relapse free survival and distance
metastases free survival time than those with low expression. Moreover,
we performed our analysis to a patient cohort of 320 patients by using
immunohistochemistry and nally 312 patients KLF11 expression level
was obtained successfully. And we found that KLF11 high expression
in BC tissue sections is strongly associated with pT classication, ki67
expression level and molecular subtype grouped by Luminal A type and
Not Luminal A type. Importantly, patients with KLF11 low expression
had signicantly improved disease-free survival time than those with high
expression, which was consistent with KMP meta-analyses. In subgroups
of this whole cohort, signicantly highlight the same DFS trends in pT1,
pN0, tumor foci ≥2 , G2-G3 patients and patients without axillary lymph
node or contrast BC, also in ER positive, PR positive, Her2 negative, Ki67
expression less than 14% and in Luminal A BC patients. Cox proportional
hazard regression analysis further identied KLF11 as an independent
factor for poor prognosis.
Conclusions: Taken together, these observations rst strongly indicated
that KLF11 might be a cancer promoter for BC and a new biomarker for
the prognosis of human breast cancer.
Disclosure Statement: is study was funded by laboratory resources.
817
Experience of One-Stage Prepectoral Reconstruction
with Polyurethane-Coated Implants in Breast Cancer
Maria Vlasova 1; Eric Saribekyan 1; Aziz Zikiryakhodzhaev 1;
Anna Sukhotko 1; Irina Shirokich 1
1Department of Oncology and Reconstructive Breast and Skin Surgery, P.
Hertzen Moscow Oncology Research Institute – branch of the National Medical
Research Radiology Center, Ministry of Health of Russia, Moscow, Russia
Purpose: Results of one-stage prepectoral reconstruction with polyure-
thane-coated implants in breast cancer.
Methods: Since 2017 to 2019 in the Department of Oncology and Recon-
structive Breast and Skin Surgery P. Hertzen Moscow Oncology Research
Institute performed 207 one-stage prepectoral reconstruction with poly-
urethane-coated implants in breast cancer.
Results: We analyzed 97 patients, 59 (60,8%) of them received radiation
therapy. e follow-up period ranged from 3 months to 2 years. Radiation
therapy in terms of combined/complex treatment 1-2 months aer sur-
gery was performed in 42 (71,2%) patients, 6-8 months aer surgery (aer
adjuvant therapy) in 18 (30,5%) patients with breast cancer.
In this group the following complications were revealed: in 28 (25,77%)
patients seroma (over 30 days), the “red breast syndrome” - 25 (25,77%)
persons, the protrusion/extrusion of the prosthesis – 16 (16,5%), the mar-
ginal necrosis/necrosis – 5 (5,15%), the infectious complications - 4 (of
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4,12%), the rippling – 6 (6,18%). e capsular contracture III-IV degree
occurred in 10 patients (16,9 %) with radiation therapy, 8 (13,5%) cases
protrusion also during radiation therapy.
Conclusions: e prepectoral breast reconstruction with a polyurethane
coating implants can be applied as an alternative submuscular location,
because 80% of patients have a good aesthetic result. According to Breast
Q the quality of life of breast cancer patients is improving.
References:
1. Nahabedian M. Y. Innovations and advancements with prosthetic breast recon-
struction. - Breast J. 2018 Jul;24(4):586-591. 1 p.
2. De Vita R., Buccheri EM. et al. Breast Reconstruction Actualized in Nip-
ple-sparing Mastectomy and Direct-to-implant, Prepectoral Polyurethane
Positioning: Early Experience and Preliminary Results. - Clin Breast Cancer,
- 2019, - 1, 2, 8 p.
Disclosure Statement: I agree
829
Detection of Sentinel Lymph Nodes in Dierent Molecular
Subtype of Breast Cancer
Aziz Zikiryakhodzhaev 1, 2; Victor Efanov 1; Liudmila Kazaryan 1, 2;
Daria Bagdasarova 1; Ilona Duadze 1, 2
1P. Hertsen MORI (Moscow, Russia), P. Hertsen MORI (Moscow, Russia), Moscow,
Russland
2SBEO HPE “I. Sechenov First MSMU” of Ministry of Health , Moscow, Russland
Purpose: To analyze the frequency of lymph nodes metastasis in dierent
molecular biological types of breast cancer.
Methods: Surgical treatment of 485 women with primary operable (cT1-
2N0M0) invasive breast cancer (BC) and clinically negative regional
lymph nodes (LN) was performed from 12.2016 to 11.2018 in National
Medical Research Radiological Center of the Russian Federation. At the
rst stage all patients underwent breast conserving surgery or mastecto-
my; the status of regional LNs was examined using a sentinel lymph node
biopsy. e age of women ranged from 22 to 81 years. Based on the rec-
ommendations of St. Gallen Consensus (2013) patients were divided into
5 groups depending on the molecular biological type.
Results: Among 485 patients with primary operable breast cancer and
clinically negative regional LN, metastasis in sentinel LN were detected
in 115 (23.7%) (p<0,005) cases. Aer dividing patients into groups it was
found that metastasis in the SLN were veried in 55 (22%) (p<0,005) cases
with luminal type A, in 47 (29.3%) (p<0,005) cases with luminal type B,
Her2/neu-negative, in 5 (17.8%) (p<0,005) with luminal type B, Her2/neu
- positive, in 5 (17%) (p<0,005) with a triple negative type and in 3 (15.7%)
(p<0,005) cases with Her2/neu overexpressing breast cancer.
Conclusions: ere were found out that despite the aggressive course
and poor prognosis Her2/neu overexpressing and triple negative breast
cancer were less associated with metastasis in regional LNs in contrast to
other molecular biological types. However there is needed to make more
detailed research with a larger amount of material for an objective judg-
ment about the eect of the tumor molecular biology on lymphogenous
metastasis.
Reference:
1. Viale G., et al. Predicting the status of axillarysentinel lymph nodes in 4351
patients with invasive breast carcinomatreated in a single institution. Cancer
2005;103(3):492–500. DOI: 10.1002/cncr.20809.PMID: 15612028.
Disclosure Statement: No
835
Intrapericardial Chemotherapy for The Management of
Malignant Pericardial Eusion of a Metastatic Breast Cancer
Patient -A Case Report
Peter Ugocsai 1; Valeria Gerthofer 1; Florian Weber 2;
Michael Rechenmacher 3; Maria Hatzipanagiotou 1; Olaf Ortmann 1;
Stephan Seitz 1
1Department of Gynecology and Obstetrics, University Medical Center
Regensburg, Regensburg, Deutschland
2Institute of Pathology, University of Regensburg, Regensburg, Deutschland
3Department of Internal Medicine III, University Medical Center Regensburg,
Regensburg, Deutschland
Purpose: Malignant pericardial eusion with hemodynamic instability is
a life-threatening condition requiring an acute intervention. Breast cancer
(BC) is the second most common malignancy with pericardial metastasis.
Due to high relapse rates aer pericardiocentesis the therapy of choice
includes a temporary pericardial drainage and the application of a local
pericardial cytotoxic treatment.
Methods: Presentation of a 48-year old patient with the symptoms of
capsular brosis 2 years aer the primary therapy of a triple positive BC
(neoadjuvant CTH [TCH], unilateral mastectomy with axillary LND,
primary reconstruction with implant, adjuvant chest and axillary irra-
diation) under ongoing adjuvant HER2-targeted and endocrine therapy
with tamoxifen. Aer surgical resection of the brotic tissue a local re-
lapse was conrmed histologically (HR-positive/HER2-negative) without
signs of metastasis in CT scan. e endocrine therapy was modied to
letrozole and GnRH-analogue. e patient was presented within 3 weeks
with orthopnea, low oxygen saturation and tachycardia. In CT scan pleu-
ral, pericardial and mediastinal metastases were detected with pleural and
pericardial eusion, causing hemodynamic instability.
Results: e insertion of a subxiphoidal pericardial drainage was carried
out (cytology: TNBC) under intensive monitoring. 3 liters of pericardial
eusion was drained over 3 days along with the local application of mi-
toxantrone. We began a systemic monotherapy with epirubicin weekly.
A nearby complete remission of the pericardial metastasis was observed
along with stable disease of all other metastases over 12 weeks of therapy.
Conclusions: Individual therapy decisions are required in case of malig-
nant pericardial eusion. 80% of the cases are clinically stable without any
need for an invasive treatment. In case of hemodynamic instability mini-
mal invasive actions should be preferred to thoracic surgery. Due to high
relapse rates the local instillation of cytotoxic substances should also be
concerned.
Disclosure Statement: no conict of interest
847
KI67 Expression in Primary Male Breast Cancer
Melanie Erices-Leclercq 1; Christian Rudlowski 1; Stephan Baldus 2;
Frank Förster 3; Lars Schröder 4; Franziska Stiller 1
1Frauenklinik, Evangelisches Krankenhaus Bergisch Gladbach, Bergisch
Gladbach, Deutschland
2Institut für Pathologie, Zytologie & Molekularpathologie, Bergisch Gladbach,
Institut für Pathologie, Zytologie & Molekularpathologie, Bergisch Gladbach,
Bergisch Gladbach
3Praxis für Gynäkologie & Geburtshilfe: Gynäkologische Onkologie &
Palliativmedizin, MVZ Flemmingstraße Poliklinik Chemnitz, Chemnitz,
Deutschland
4Frauenlinik, Klinikum Hanau GmbH Klinik für Gynäkologie und Geburtshilfe,
Hanau, Deutschland
Purpose: Male breast cancer (MBC) is a rare disease. Approximately 1 %
of breast carinoma are diagnosed in men. Only few studies with small
patient numbers are available. Guidelines for diagnosis and treatment of
MBC are derived from female breast cancer. Both diseases share similar-
ities but there are signicant dierences regarding risk factors and prog-
nosis. In this study we evaluated the clinical signicance of proliferation
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factor Ki67 for MBC. e aim was to dene optimal Ki-67 scoring meth-
ods and cut-o values as prognostic marker for MBC.
Methods: Tumor tissue was obtained from 104 patients with primary
MBC. Clincopathologicial characteristics including follow-up data were
sampled and investigated. Ki67 expression was evaluated in paran-em-
bbeded specimen by using standard immunohistochemistry. We applied
three methods to analyse Ki67 expression: (1) Ki67 expression as percent-
age of nuclear Ki67 tumor staining on average (TA), (2) Ki67 expression
at the tumor border (TB) and (3) hotspots of Ki67 expression (HS). Sta-
tistical analysis was performed using receiver operating characteristics
(ROC) to determine specic cut o points for each method. Based on the
calculated cut o points, clinicopathological characteristics and overall
survival (OS) univariate and multivariate analysis as well as cox regression
were performed.
Results: Ki67 staining was successful in all cases. Ki67 expression cut o
points were 13.5 % for TA, 17.5 % for TB and 22.5 % for HS. Ki67 expres-
sion correlated with tumor size, nodal stage and tumor grading. All cut o
points were signicantly associated with OS. In multivariate analysis only
Ki67 TA and TB were statistically correlated to OS.
Conclusions: Ki67 expression measured by TA and TB are suitable to pro-
vide information regading OS in primary MBC. Patients with Ki67 less
than 13.5 % (TA) and 17.5 % (TB) showed signicant improved OS. Our
restrospective study illustrates Ki67 expression to be a promising prog-
nostic parameter in MBC.
Disclosure Statement: No disclosure
Cancer of Unknown Primary (CUP)
Cancer Prevention
Poster
88
Selection Bias in Observational Studies Evaluating Cancer
Screening Tests and Examinations
Jonas Czwikla 1; Ingo Langner 2; Ulrike Haug 2
1Universität Bremen, SOCIUM Forschungszentrum Ungleichheit und
Sozialpolitik, Bremen, Deutschland
2Leibniz-Institut für Präventionsforschung und Epidemiologie – BIPS, Bremen,
Deutschland
Purpose: We previously found that i) mammography screening partici-
pants and nonparticipants are not comparable in terms of 4-year all-cause
mortality, and ii) comorbidity measures determined based on claims data
are insucient to control for this selection bias [1]. We aimed to extend
these analyses to cervical, prostate, colorectal, and skin cancer screening.
Methods: Using claims data of the BARMER covering the years from 2007
to 2017, participants and nonparticipants of the Pap smear, digital rec-
tal exam, fecal occult blood test (FOBT)/colonoscopy, and visual whole-
body skin examination were identied. For each cancer screening, Cox
proportional hazards regression was used to compare all-cause mortality
between participants and nonparticipants within ≤ 7 years. We adjusted
for sex (if applicable), age (if applicable), residence, and comorbidity.
Results: Claims data of 5,765,852 persons were analyzed. e crude haz-
ard ratios (HRs) for death from any cause for participants vs. nonpar-
ticipants of the respective cancer screening were 0.22 (99.9% condence
interval 0.22-0.23) for Pap smear, 0.88 (0.86-0.89) for digital rectal exam,
0.51 (0.45-0.58) for FOBT/colonoscopy, and 0.70 (0.70-0.71) for skin ex-
amination. e adjusted HRs were 0.57 (0.56-0.58), 0.69 (0.68-0.70), 0.57
(0.50-0.65), and 0.75 (0.74-0.76), respectively.
Conclusions: Because cancer screening is expected to reduce all-cause
mortality by only 1-3% [2], the observed lower mortality among screening
participants must be due to selection bias. e extent of this bias diers
considerably between cancer screening tests and examinations. Obser-
vational studies evaluating the eectiveness of cancer screening need to
apply appropriate methods for controlling selection bias. Controlling only
for sex, age, residence, and comorbidity appears to be insucient.
References:
1. Czwikla J et al.: J Clin Epidemiol 2018;104:1-7.
2. Stang A et al.: Dtsch Arztebl Int 2018;115(29-30):481-6.
Disclosure Statement: No conict of interest.
339
Regional Disparities of Cancer Prevention – the Case
of Thuringia
Sebastian Henn 1; Jutta Hübner 2; Susann Schäfer 1; Anika Zorn 1
1Institut für Geographie, Friedrich-Schiller-Universität, Jena, Deutschland
2Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Deutschland
Purpose: It is a medically undisputed fact that physical activity, a healthy
nutrition and the minimization of risk factors (e.g. smoking, drinking)
form the three most important pillars of cancer prevention. Although
these factors are mainly determined by personal factors, there is no doubt
that regional infrastructures play an important role in cancer prevention.
Such infrastructures include facilities that address the above-mentioned
pillars through oering specialized services related to physical activity,
healthy eating or individual control of risk factors. Cancer prevention in-
frastructures vary considerably from one region to another; in particular,
signicant dierences can be expected between urban and rural areas.
is paper aims to compare the current state of regional cancer prevention
infrastructure on municipal level.
Methods: Methods of empirical social research (expert interviews,
semi-standardized surveys)
Results: Drawing on relevant statistics and other sources, we develop an
integrated indicator that combines information on the availability of pub-
lic and non-public prevention infrastructures, e.g. sports facilities, access
to regional unprocessed food and drug prevention services.
Conclusions: is indicator can serve as a basis for local actors to control
and further develop cancer prevention on a regional level. Although we
use the above indicator to characterize the current prevention infrastruc-
tures in uringia; the approach proposed can be applied to other regions
in Germany and/or abroad.
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382
Green Tea Extract Versus Placebo for the Prevention
of Colorectal Adenomas: a Randomized, Controlled
Trial - Miracle Trial
Stefan Menzler 1; Thomas Seuerlein 2; Helmut Messmann 3;
Gerhard Kleber 4; Alexander Zipprich 5; Stefanie Frank-Gleich 6; Hana
Algül 7; Klaus Metter 8; Frank Odemar 9; Theodor Heuer 10; Ulrich Hügle 11;
Rüdiger Behrens 12; Lukas Perkhofer 2; Catharina Scholl 13;
Katharina Schneider 13; Friederike Rohlmann 14; Rainer Muche 14;
Julia Stingl 15, 16; Thomas J. Ettrich 2
1Praxis Klinik Marburg, Marburg, Deutschland
2Ulm University Hospital, Department of Internal Medicine I, Ulm, Deutschland
3Augsburg University Hospital, Department of Internal Medicine III, Augsburg,
Deutschland
4Ostalb-Klinikum Aalen, Department of Internal Medicine I, Aalen, Deutschland
5Martin-Luther-University Halle-Wittenberg, Department of Internal Medicine I,
Halle (Saale)
6Private Practice Oncology, Halle (Saale), Deutschland
7Technical University Munich, Department of Internal Medicine I, München,
Deutschland
8Alb-Fils-Kliniken, Department of Gastroenterology, Göppingen, Deutschland
9Amos Klinikum Bernburg, Department of Internal Medicine, Bernburg (Saale)
Deutschland
10St. Bernhard-Hospital, Department of Internal Medicine I, Kamp-Lintfort,
Deutschland
11Krankenhaus Köln-Holweide, Department of Gastroenterology, Köln,
Deutschland
12Gastroenterologisch-onkologische Praxisklinik, Private Practice, Halle (Saale),
Deutschland
13Federal Institute of Drugs and Medical Devices, Research Division, Bonn,
Deutschland
14Ulm University, Institute of Epidemiology and Medical Biometry, Ulm,
Deutschland
15University of Bonn Medical School, Centre for Translational Medicine, Bonn,
Deutschland
16Federal Institute for Drugs and Medical Devices, Bonn, Deutschland
Purpose: Prevention of colorectal adenomas (CA) is likely to prevent col-
orectal cancer (CRC). Nutri- or chemoprevention of CRC is not yet es-
tablished. NSAIDs show some benet but also increase the bleeding risk.
Preclinical and small clinical trials suggest that epigallocatechingallate
(EGCG), a major polyphenol in green tea, has a good safety prole and
antineoplastic eects in the large bowel, but there are no data from large
trials. MIRACLE enrolled 1001 patients to examine the eect of a three
year intake of ECGC on the recurrence of CA aer polypectomy.
Methods: Double-blinded, placebo-controlled trial, 41 German centers,
recruitment 12/2011-6/2015. Patients aged 50-80 years who underwent
polypectomy within the last 6 months and tolerated EGCG well during a
one month run-in were randomized to standardized decaeinated EGCG
(150 mg bid) or placebo for 3 years. Primary endpoint: Incidence of CA
at the 3 year follow-up colonoscopy. Secondary endpoints: Occurrence,
number, localization, size, histological subtype of CA, frequency of CRC
and biomarker. Strata: Study center and low-dose aspirin (≤100 mg/d).
Results: Clinical parameters were well balanced. Primary endpoint was
analysed in the modied ITT set (modITT; n=309 patients in EGCG,
n=323 in placebo group giving informed consent and undergoing 3 year
follow up colonoscopy). n=102 patients in the EGCG and n=103 in the
placebo group were excluded due to missing follow up colonoscopy. In-
cidence of one or more CA aer 3 year of placebo or EGCG 150 mg bid
was 55.7 % and 51.1%, respectively (one sided adj. P=0.077, adj. RR 0.904)
in the modITT. In the PP-set constituting all modITT patients complet-
ing the study without major protocol violations the respective gures
were 54.3 % in the placebo and 48.3% in the EGCG group (one sided adj.
P=0.058, adj. RR 0.883). ere were no safety issues and no major dier-
ences in AEs between EGCG and placebo during the randomized phase.
Conclusions: 300 mg EGCG per day was well tolerated and showed a
trend towards a preventive eect on CA in the large bowel though not
statistically signicant.
432
Reduction of Genital Warts and Precancerous Lesions in HPV
Vaccinated Young Women in Bavaria
Sandra Fett 1; Martin Tauscher 1; Antonius Schneider 2; Stefanie Klug 3
1Kassenärztliche Vereinigung Bayerns (KVB)
2Institut für Allgemeinmedizin und Versorgungsforschung, , Klinikum Rechts der
Isar, Technische Universität München
3Lehrstuhl für Epidemiologie, Fakultät für Sport- und
Gesundheitswissenschaften, Technische Universität München
Purpose: HPV (Human Papillomavirus) vaccination has been available
in Germany since 2006 and was recommended by the Standing Commit-
tee on Vaccination (STIKO) in 2007 for girls and in 2018 for boys. e
vaccine should be given before the rst sexual contact in order to exclude
a prior exposure to the infection. e HPV vaccine is considered highly
eective and safe. Data from Australia, where vaccination rates are at 80%,
show a marked reduction in the rates of genital warts and precancerous
lesions of the cervix uteri in vaccinated young women. In Germany, 44.6%
of 17-year-old girls were fully vaccinated in 2015, while vaccination rates
were lower in Bavaria.
Methods: We assessed data of legally insured girls from the database of
the Bavarian Association of Statutory Health Insurance Physicians (KVB).
Vaccination coverage trends were evaluated cross-sectionally and longitu-
dinally. Age at vaccination and type of vaccine administered were inves-
tigated. Trends regarding diagnosis of genital warts (ICD-10: A63.0) and
precancerous lesions of the cervix uteri (ICD-10: N87.1, N87.2 and D06)
between vaccinated and unvaccinated young women were also evaluated.
Results: More than 350,000 girls were vaccinated against HPV in Ba-
varia from 2008 until 2018. e overall vaccination rate was 46.7%. In
2017, 51% of 18-year old girls were vaccinated at least once against HPV.
e number of pediatricians delivering vaccination showed a signicant
increase in comparison to gynecologists and general practitioners. e
vaccination rates increased signicantly over the years, but with strong
regional dierences within Bavaria. A reduction in genital warts as well
as precancerous lesions is already visible in young women who have been
vaccinated against HPV.
Conclusions: e rst evaluations on the use of HPV vaccine in Bavaria
show a promising decline in the diagnosis of genital warts and precan-
cerous lesions in vaccinated young women. However, a clear increase in
vaccination rates is necessary.
548
Hasco Study Protocol: Pilot Study for Systematic HPV
Self-Sampling for Non-Responders to the Cervical Cancer
Screening Program
Matthias Jentschke; Johanna Kampers; Peter Hillemanns
Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule
Hannover (MHH), Hannover, Deutschland
Purpose: In this pilot study we will evaluate a systematic approach to-
wards human papillomavirus (HPV) self-sampling for non-responders
to the German cervical cancer screening program. In 2020, an organized
screening program with co-testing (HPV test + cytology) in 3-yearly in-
tervals will be started. In the past, the participation rate was around 70%
in a time frame of three years. e non-participators are at higher risk to
develop cervical carcinoma. Previous studies have shown an improving
number of patients participating when being re-invited. e willingness to
participate in self sampling programs is even higher. Based on this infor-
mation, the Hannover Self-Collection study was designed to examine the
response rate and practicability of a systematic self-sampling approach.
Methods: 20.000 women aged 30 to 65 years living in the city and re-
gion of Hannover, Lower Saxony are randomly included. 10.000 women
directly receive a self-sampling kit, the other 10.000 a letter of informa-
tion and option to participate in the study (opt-out vs. opt-in strategy).
Stratications will be made by age (7 cohorts) and area of living (city vs
rural). Women tested positive for high-risk HPV (PCR-based HPV assay)
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are prompted to get a cytological smear by their gynecologist. Women
with normal cytology will be re-checked aer 6 months. Suspicious cy-
tology results lead to an immediate colposcopy. Further treatment will be
performed according to the German S3-guideline prevention of cervical
cancer.
Results: We designed a prospective randomized study to primarily exam-
ine: I) the participation rate (opt-out vs. opt-in model), II) the compliance
aer a positive HPV test, III) the comparison between two self-sampling
gadgets, IV) triaging the samples by new DNA-methylation tests.
Conclusions: To get hold of non-responders to cervical cancer screen-
ing programs; self-sampling for HPV is a promising option. Aim of this
study is to generate an overall recommendation to improve cervical can-
cer screening in Germany; especially for non-responders. is study is
supported by Deutsche Krebshilfe.
609
Protecting Young athletes from UV-Radiation – a Program
for Sports Schools
Friederike Stölzel 1; Michaela Wol 1; Vera Fieber 1; Melanie Glausch 1;
Eckhard Breitbart 2; Martin Bornhäuser 1, 3, 4; Nadja Seidel 1
1Universitätsklinikum Carl Gustav Carus, Universitäts Krebscentrum (UCC),
Dresden, Deutschland
2Arbeitsgemeinschaft Dermatologische Prävention (ADP) e. V., Hamburg,
Deutschland
3Universitätsklinikum Carl Gustav Carus Dresden, Medizinische Klinik und
Poliklinik I, Dresden, Deutschland
4Nationales Centrum für Tumorerkrankungen (NCT), Dresden, Deutschland
Purpose: e incidence of melanoma and nonmelanoma skin cancer has
increased rapidly.1 Overexposure to ultraviolet radiation is an established
risk factor for the development of melanoma. Due to their intensive sun
exposure, student-athletes (SAs) performing outdoor sports have an
increased risk for developing skin cancer. 2 Using participatory program
planning (PPP), the authors developed a UV-protection-program (UPP)
that aims at supporting sports schools in establishing UV-protection
strategies.
Methods: To ensure feasibility, UPP was developed in 2019, closely coop-
erating with students (N=30), parents (N=5), teachers (N=8) and trainers
(N=7) of Sportgymnasium Neubrandenburg in 3 focus groups as well as
following WHO-recommendations for sun-protection at schools.
Results: In using PPP and working with focus groups-results, UPP could
be constructed to meet sports schools’ needs, for example employing di-
rective sun-protection briefs and including core values stated most fre-
quently by young athletes. UPP now consists of a project kit containing
videospots with tailored messages targeting students, trainers, teachers
and parents, as well as posters and a manual about sun-protection and
details on its successful implementation.
Conclusions: PPP has shown to be an eective and valuable method in
developing UPP for sports schools. Feasibility and acceptance of UPP will
be evaluated in September 2019 at Sportgymnasium and Sportoberschule
Dresden.
References:
1. Institut für Krebsepidemiologie e.V. (2018). Zahlen Zu Hautkrebs in Deutsch-
land.
2. Ally, M., et al. (2018). Promoting sunscreen use and sun-protective practices
in NCAA athletes: Impact of SUNSPORT educational intervention for
student-athletes, athletic trainers, and coaches. J Am Acad Dermatol, 78,
2:289-292.e2.
Disclosure Statement: No conicts of interest.
671
Update on HPV-attributable Cancer in Germany 2016
Nina Buttmann-Schweiger; Klaus Kraywinkel
Zentrum für Krebsregisterdaten (ZfKD), Robert Koch-Institut, Berlin,
Deutschland
Purpose: HPV-attributable cancer is a preventable disease. An estimat-
ed ~7.600 people in Germany were predicted to be diagnosed with an
HPV-attributable cancer1,2. e proportion of oropharyngeal (OP) squa-
mous cell carcinoma (SCC) was assumed to be relatively low (16-20%)
based on a pooled analysis of European study results. As country specic
results on the changing epidemiology of oropharyngeal (OP) squamous
cell carcinoma (SCC) in Germany is available3, our aim was to update pre-
vious estimates on the incidence of HPV-attributable cancer for Germany.
Methods: Nationwide cancer incidence on HPV-related SCC for 2016 was
calculated based on estimates of cancer incidence rates from the Center
for Cancer Registry Data for Germany. Proportions of cancers attributable
to HPV-infection (HPV-AF) were calculated according to previously pub-
lished methods2, taking new country specic results on HPV-prevalence
in OPSCC into account.
Results: Two clinical studies from Germany attribute >50% of most re-
cently diagnosed OPSCC to HPV (years of diagnosis 2013/2015). When
taking the country specic prevalence in OPSCC into account, the HPV-
AF in OPSCC will be more than twice as high as previously reported. e
total number of HPV-attributable cancer in Germany then approaches
10.000 new cases a year.
Conclusions: Previous estimates attributed a signicantly lower propor-
tion of OPSCC to HPV than most recent study results from two single
medical institutions in Germany suggest. Although the calculation of
HPV-related cancer burden remains methodologically challenging, recent
evidence indicates that oropharyngeal cancer increasingly contributes to
the burden of cancer. e HPV-AF for OPSCC in Germany will best be es-
timated by direct testing of HPV DNA/p16 overexpression/E6-E7 mRNA
expression in continuous representative sentinel sampling of tumor tissue
for monitoring the eects of HPV-vaccination in the German population.
References:
1. DOI: 10.3238/arztebl.2018.0586;
2. DOI 10.1186/s12885-017-3678-6;
3. DOI: 10.1002/cam4.2039
Disclosure Statement: no conicts of interest
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 31
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2018
Index
2018
814
Results of Intensied Breast Cancer Screening in Women
After Treatment for Hodgkin's Lymphoma in Childhood
and Adolescence
Kerstin Rhiem 1; Sarah Schott 2; Dorothee Speiser 3; Joke Tio 4;
Marion Kiechle 5; Susanne Briest 6; Anne-Sophie Vesper 7; Karin Kast 8;
Marion von Mackelenbergh 9; Elena Leinert 10; Christoph Engel 11;
Rita K Schmutzler 1
1Zentrum Familiärer Brust- und Eierstockkrebs, Centrum für Integrierte
Onkologie (CIO), Universitätsklinikum Köln, Köln, Deutschland
2Universitäts-Frauenklinik, Heidelberg, Deutschland
3Charite - Campus Mitte Klinik für Gynäkologie und Gynäkologische Onkologie
m.S. Laparoskopische Tumorchirurgie, Berlin, Deutschland
4Senologie, Universitätsklinikum Münster, Münster
5Klinik und Poliklinik für Frauenheilkunde, Technische Universitäts München,
München
6Brustzentrum, Universitätsklinikum Leipzig, Leipzig
7Frauenklinik, Universitätsklinikum Düsseldorf, Düsseldorf
8Klinik und Poliklinik für Frauenheilkunde, Universitätsklinikum Dresden,
Dresden
9Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-
Holstein, Campus Kiel, Kiel
10Universitäts-Frauenklinik Ulm, Ulm
11Institut für Medizinische Informatik, Statistik und Epidemiologie,
Universitätsklinikum Leipzig, Leipzig
Purpose: Treatment of pediatric Hodgkin´s lymphoma (HD) by radio-/
chemotherapy lead to more than 90% survivors within at least 20 years.
However, patients suer from long-term sequelae particularly including
former radiation elds (e.g. secondary breast cancer/sBC). Since 2012 pa-
tients from HD studies (HD-78 to HD-95/Intervall) received the oer to
participate in the structured surveillance program for breast cancer (IFP)
within the German Consortium for Hereditary Breast and Ovarian Can-
cer (GC-HBOC).
Methods: We aimed to prospectively evaluate the ecacy of the iFE in fe-
male HD patients who had received radiation to the breast at young ages.
Within the “GPOH-HD-Spätfolgen” research project 534 women of a co-
hort study with more than 30 years´ follow up were still alive in 2012. 224
of them participated in the IFP.
Results: Median age at time of HD diagnosis was 16.3 years. By September
2019, 33 sBC had been diagnosed at a median age of 41.7y (range 26-56y).
Median Interval from HD to sBC was 23.4y. 22 prevalent (66.7%) and 11
incident (33.3%) cases of sBC were diagnosed. 10 of 11 (90%) incident
cases were detected in early stages (pTis/1a-c, pN0) while 8 of 22 (36.4%)
prevalent cases were diagnosed in stage pT2 and/or pN+ and one patient
was primarily metastasized. e majority of tumors were ductal invasive
(85%, n=22 von 26), G1-2 (72%, n=21 von 29) and hormone receptor pos-
itive (81%, n=25 von 31).
Conclusions: Women who received radiation to the breast for HD at
young ages face a signicantly elevated risk for sBC compared to risk-ad-
justed general population and should be informed about the IFP at the
centers of the GC-HBOC. In further studies we will investigate the role of
genetic risk factors in the pathogenesis of sBC.
Central Nervous System Tumors
Poster
126
Inhibition of the DNA Damage Response in Neuroblastoma
Cells Aects Sensitivity to Platinum Compounds
Katharina Roquette; Stefanie Gaertner; Gerhard Fritz
Institut für Toxikologie, Heinrich-Heine Universität Düsseldorf, Düsseldorf,
Deutschland
Neuroblastoma (NB) are one of the most common malignant paediatric
brain tumors. Patients treated with aggressive platinum-based chemo-
therapy oen suer from long-term sequelae. Additionally, developed
drug resistance oen limits therapeutic ecacy. Here, we target the DNA
damage response (DDR) of NB cells diering in their N-myc status in or-
der to modulate their sensitivity to platinum compounds. Additionally, we
comparatively investigated the platinum compound response of NB cells
and cisplatin (CisPt) selected drug resistant NB variants. e DDR was
modulated by pharmacological inhibition of checkpoint kinases (CHK
1/2) and poly(ADP-ribose)-polymerase 1 (PARP 1) with LY2603618 or
Olaparib, respectively.
Cell viability was determined by using the Alamar Blue assay. Alterations
in cell cycle progression were assayed by ow cytometric analysis. e for-
mation of Pt-(GpG) intrastrand crosslinks was determined via Southwest-
ern blot. e amount of DNA double-strand breaks (DSBs) was quantied
by measuring the levels of nuclear γH2AX (S139 phosphorylated H2AX)
and 53BP1 foci via immunocytochemistry. Mechanisms of the DDR were
analysed by Western blot and the expression of CisPt-related susceptibili-
ty factors by quantitative realtime PCR.
N-myc amplied IMR-32 cells revealed an increased sensitivity to plati-
num compounds as well as to the pharmacological inhibitors in compari-
son to the N-myc nonamplied SH-SY5Y cells. Upon months-long CisPt
selection, CisPt resistant SH-SY5YR and IMR-32R variants were isolated,
which revealed up to 4-fold increased CisPt resistance as compared to
their corresponding wild-types. e resistant variants were cross-resistant
to carboplatin (CarboPt) as well as to LY2603618 and Olaparib. Pretreat-
ment with subtoxic concentrations of the inhibitors increased the sensitiv-
ity to CisPt in both cell lines.
Based on the data, we conclude, that pharmacological modulation of
the DDR/DNA repair is useful for targeting CisPt resistant NB cells
and, furthermore, to improve their responsiveness to platinum-based
chemotherapy.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts32
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2018
Index
2018
282
Activity of Larotrectinib in TRK Fusion Cancer Patients with
Brain Metastases or Primary Central Nervous System Tumors
Serge Leyvraz 1; Alexander Drilon 2; Steven G Dubois 3; Anna F Farago 4;
Birgit Geoerger 5; Juneko E Grilley-Olson 6; David S Hong 7;
Davendra Sohal 8; Cornelis M van Tilburg 9; David S Ziegler 10; Nora C Ku 11;
Michael C Cox 11; Shivani Nanda 12; Barrett H Childs 12; Francois Doz 13
1Charité Comprehensive Cancer Center, Charité Berlin, Berlin, Deutschland
2Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College,
New York, United States
3
Dana-Farber/Boston Childrens Cancer and Blood Disorders Center, Boston,
United States
4Department of Medicine , Massachusetts General Hospital, Boston,
United States
5Gustave Roussy, Department of Pediatric and Adolescent Oncology,
Université Paris-Sud, Université Paris-Saclay, Villejuif, Frankreich
6University of North Carolina Hospitals, Chapel Hill, United States
7The University of Texas MD Anderson Cancer Center, Houston, United States
8Cleveland Clinic, Cleveland, United States
9Hopp Childrens Cancer Center Heidelberg (KiTZ), Heidelberg University
Hospital and German Cancer Research Center (DKFZ), Heidelberg, Deutschland
10Sydney Childrens Hospital, Randwick, Australien
11Loxo Oncology, Inc., San Francisco, United States
12Bayer U.S. LLC, Whippany, United States
13Institut Curie, SIREDO Oncology Center (Care, Innovation and research for
children and AYA with cancer), Paris Descartes University, Paris, Frankreich
Purpose: TRK fusions are oncogenic drivers of a variety of cancers, many
of which can involve the central nervous system (CNS). Larotrectinib is
a FDA-approved selective TRK inhibitor for the treatment of TRK fusion
cancer. While larotrectinib has been shown to cross the blood–brain bar-
rier, its clinical activity in a series of TRK fusion cancers with primary or
metastatic intracranial disease has not been described.
Methods: Patients (pts) with non-primary CNS solid tumors with brain metas-
tases, or primary CNS tumors harboring a TRK fusion treated with larotrectinib
in two clinical trials (NCT02637687, NCT02576431) were identied. Larotrec-
tinib was administered until disease progression, withdrawal, or unacceptable
toxicity. Disease status was investigator-assessed (RANO, RECIST).
Results: 24 pts were identied: 6 non-primary CNS solid tumors (4 lung
cancer, 2 thyroid cancer; fusion type: 2 ETV6-NTRK3, 2 SQSTM1-NTRK3,
1 EPS15-NTRK1; 1 TPR-NTRK1; age range 25–79 y) and 18 primary CNS
tumors (6 glioblastoma, 4 glioma, 3 glioneuronal, 3 NOS, 2 astrocytoma;
13 fusion genes involving NTRK2, and 2 each NTRK1 and NTRK1; aged
2–79 y). In 5 pts with non-primary CNS tumors evaluable for response,
the best objective response to therapy was PR in 3 (60%, 1 pending conr-
mation), SD in 1 (20%). Duration of response ranged from 9+ to 13 mo. In
the 18 pts with primary CNS tumors, the best overall response to therapy
was CR in 2 pts, PR in 3 pts, for an objective response rate of 36%. 9 pts
(64%) had SD. Disease control ≥ 24 w was seen in 10 pts (71%). Duration
of treatment ranged from 0.03+ – 16.6+ mo.
Conclusions: Larotrectinib is active in pts with TRK fusion cancers with
intracranial disease. Conrmed responses and durable disease control were
seen in metastatic disease and primary CNS tumors of various histologies.
ese results further support expanded testing for TRK fusions across all
cancers, including primary CNS tumors.
© 2019 American Society of Clinical Oncology, Inc. Reused with permis-
sion. is abstract was accepted and previously presented at the 2019 Asco
Annual Meeting. All rights reserved.
Disclosure Statement:
Serge Leyvraz reports personal fees from Immunocore, and Bayer outside the
submitted work.
Alexander Drilon reports HONORARIA/ADVISORY BOARDS: Ignyta/
Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP erapeutics,
AstraZeneca, Pzer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui
erapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health; ASSOCIATED
RESEARCH PAID TO INSTITUTION: Pzer, Exelixis, GlaxoSmithKlein, Teva,
Taiho, PharmaMar; RESEARCH: Foundation Medicine; ROYALTIES: Wolters
Kluwer; OTHER: Merck - Food/Beverage, Puma - Food/Beverage, and CME
HONORARIA: Medscape, OncLive, PeerVoice, Physicians Education Resources,
Targeted Oncology, Research to Practice.
Steven G. DuBois reports Loxo: consultancy and travel expenses, and Roche:
travel expenses.
Anna F. Farago reports Research support ‒ Bayer Healthcare, Loxo Oncology,
Inc., Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, PharmaMar,
Merck, Ignyta, Amgen, Novartis; Consultant ‒ Bayer Healthcare, Loxo Oncology,
Inc., Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, PharmaMar,
Boehringer Ingelheim, and Honorarium – Dava Oncology, Clinical Care Options,
Medical Learning.
Birgit Geoerger none.
Juneko E. Grilley-Olson none.
David S. Hong reports Research/Grant Funding: AbbVie, Adaptimmune, Amgen,
Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate erapeutics, Genentech,
Genmab, Ignyta, Innity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati,
MiRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pzer, Seattle
Genetics, Takeda; Travel, Accommodations, Expenses: LOXO, MiRNA, ASCO,
AACR, SITC, Genmab; Consulting or Advisory Role: Alpha Insights, Axiom,
Adaptimmune, Baxter, Bayer, Genentech, Glg, Group H, Guidepoint Global,
Innity, Janssen, Merrimack, Medscape, Numab, Pzer, Seattle Genetics, Takeda,
Trieza erapeutics, and Other ownership interests: Molecular Match (Advisor),
OncoResponse (founder), Presagia Inc (Advisor).
Davendra Sohal reports Consulting advisory role, Perthera, Ability Pharma;
Honoraria, Foundation Medicine, and Research funding, Novartis, Cellgene,
OncoMed, Bayer, Genentech, Bristol-Myers Squibb, Agios, Incyte, Loxo.
Cornelis M. van Tilburg reports Bayer: advisor, and Novartis: advisor.
David S. Ziegler nothing to disclose.
Nora C. Ku is an employee of Loxo Oncology Inc.
Michael C. Cox was an employee of Loxo Oncology Inc.
Shivani Nanda is an employee of Bayer.
Barrett H. Childs is an employee of Bayer.
Francois Doz reports BAYER: travel expenses, advisory board, and ROCHE:
advisory board.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 33
Inhalt
2018
Index
2018
386
Targetable FGFR3 Fusions and Novel FGFR3 Mutations
in Glioma
Jens Schittenhelm 1, 2, 3; Lukas Ziegler 2; Michel Mittelbronn 4, 5, 6, 7;
David Capper 8; Isabel Burghardt 1, 9; Antti Poso 10, 11; Saskia Biskup 12;
Marko Skardelly 1, 9, 13; Ghazaleh Tabatabai 1, 3, 9
1Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart,
University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,
Tuebingen, Deutschland
2Department of Neuropathology, Institute of Pathology and Neuropathology,
University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,
Tuebingen, Deutschland
3German Consortium for Translational Cancer Research (DKTK), DKFZ partner
site Tuebingen, Tuebingen, Deutschland
4Luxembourg Centre of Neuropathology (LCNP), Dudelange, Luxemburg
5Centre for Systems Biomedicine (LCSB), University of Luxembourg,
Esch-sur-Alzette, Luxemburg
6National Center of Pathology (NCP), Laboratoire National de Santé (LNS),
Dudelange, Luxemburg
7Department of Oncology (DONC), Luxembourg Institute of Health (LIH),
Luxembourg, Luxemburg
8Institute for Neuropathology, Charite, Berlin, Deutschland
9Interdisciplinary Division of Neurooncology, Hertie-Institute for Clinical Brain
Research, Tuebingen, Deutschland
10Department of Internal Medicine VIII, University Hospital of Tuebingen,
Eberhard Karls University Tuebingen, Tuebingen, Deutschland
11School of Pharmacy, University of Eastern Finland, Kuopio, Finnland
12CeGaT GmbH and Praxis für Humangenetik, Tuebingen, Deutschland
13Department of Neurosurgery, University Hospital of Tuebingen, Eberhard Karls
University Tuebingen, Tuebingen, Deutschland
Purpose: Fibroblast growth factor receptor (FGFR) inhibitors are cur-
rently in clinical development. A subset of IDH wildtype glioblastomas
contain fusion genes between FGFR3 and transforming acidic coiled-coil
protein 3 (TACC3). e resulting increase in FGFR3 expression is con-
sidered as a marker to detect FGFR3 fusions in gliomas. e aim of the
present study was (i) to investigate alterations in FGFR3 in the Tübingen
glioma cohort and (ii) to evaluate the role of FGFR3 immunohistochem-
istry in addition to targeted NGS gene panel sequencing and RT-PCR.
Methods: FGFR 3 immunohistochemistry (IHC) screening was carried
out in 548 glioma samples using tissue microarrays. e results were val-
idated in external cohorts with a total of 326 patients. RT-PCR screen-
ing and IHC was performed in 101 consecutive sampled glioblastomas
to determine the frequency of FGFR3 –TACC3 fusions. Further targeted
NGS panel sequencing was carried out in 74 samples. e eect of a novel
specic mutation was further studied by molecular modelling.
Results: e spectrum of molecular alterations that we detected included
FGFR3 fusions, FGFR3 amplication and FGFR3 gene mutations. FGFR3
fusions were associated with strong FGFR3 protein expression and dis-
tinct histological patterns. Molecular modelling of the novel mutation
suggests that this molecular event leads to an activating FGFR3 kinase
function. A detailed analysis will be presented.
Conclusions: Gliomas may carry more than one FGFR3 alteration in
the same tumor. FGFR3 IHC might be a useful marker to identify FG-
FR3-TACC3 fusions in IDH-wildtype tumors and could thus be further
included in the regular IHC diagnostic algorithm to detect therapeutic
targets.
Disclosure Statement: GT served on Advisory Boards of BMS, MSD and AbbVie;
received research and/or travel grants from Roche Diagnostics, Novocure and
Medac, received speakers` fees from Medac, Novocure.
400
Personalized Medicine for Neuro-Oncology Patients:
Implementation and Outcome of the Molecular Tumor
Board Tuebingen
Isabel Burghardt 1, 2, 3; Patrick Strohmaier 2, 3; Mirjam Renovanz 1, 2, 3;
Jens Schittenhelm 1, 3, 4; Kirsten Wyrwich 2; Kristina Ruhm 3; Janina Beha 3;
Yvonne Möller 3; Özner Önur 3; Saskia Biskup 5; Cristiana Roggia 6;
Michael Bitzer 3, 7; Marcos Tatagiba 1, 2, 3; Daniel Zips 3, 8; Nisar Malek 3, 7;
Ghazaleh Tabatabai 1, 2, 3
1Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart,
University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,
Tuebingen, Deutschland
2Interdisciplinary Division of Neurooncology, Hertie-Institute for Clinical Brain
Research, Tuebingen, Deutschland
3Center for Personalized Medicine, Eberhard Karls University of Tuebingen,
Tuebingen, Deutschland
4Department of Neuropathology, Institute of Pathology and Neuropathology,
University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,
Tuebingen, Deutschland
5CeGaT GmbH and Praxis für Humangenetik, Tuebingen, Deutschland
6Institute of Medical Genetics and Applied Genomics, University Hospital of
Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Deutschland
7Department of Internal Medicine I, University Hospital of Tuebingen, Eberhard
Karls University Tuebingen, Tuebingen, Deutschland
8Department of Radiation Oncology, University Hospital of Tuebingen, Eberhard
Karls University Tuebingen, Tuebingen, Deutschland
Purpose: e Molecular Tumor Board (MTB) at the University Hospital
Tuebingen has been established in 2016 to discuss molecular data-driv-
en personalized therapeutic strategies for all tumor patients. e current
study aims at retrospectively reviewing the MTB experience so far for
neuro-oncology patients with a particular focus on feasibility, work ows
for molecular diagnostics, review of frequent molecular patterns and clin-
ical outcome.
Methods: Medical records from MTB neuro-oncology patients from
April 2016 – August 2019 were reviewed. e retrospective study was ap-
proved by the ethical board. We discussed molecular proling reports in
the MTB, evaluated the evidence for actionability of molecular alterations
and recommended molecular data-driven therapeutic strategies.
Results: So far, around 300 neuro-oncology patients with dierent his-
tological entities (primary and metastatic tumors) were presented in the
MTB. Molecular diagnostics included gene panel sequencing, transcrip-
tome analysis and immunohistochemical staining of associated targets in
selected cases. Actionable alterations were frequently detected. A precise
analysis will be presented. In the subgroup of glioblastoma patients, mo-
lecular alterations in the CDKN2A/2B and in the PTEN gene occurred
frequently. Immunohistochemical evaluation of associated targets was
included with antibodies detecting relevant downstream targets. Genetic
changes and protein data in the associated cellular pathways will be cor-
related. e nal analysis of therapeutic strategies and clinical outcome
data will be presented.
Conclusions: A personalized medicine program is feasible for neuro-on-
cology patients, particularly in the absence of further treatment options or
matching clinical trials. e MTB ensures an appropriate interdisciplinary
discussion of tumor molecular proles, therapeutic decisions and docu-
mentation of outcome.
Disclosure Statement: GT: served on Advisory Boards of BMS, MSD, AbbVie;
research and/or travel grants: Roche, Novocure, Medac, speakers` fee: Medac,
Novocure.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts34
Inhalt
2018
Index
2018
402
Ecacy of Entrectinib in Patients (PTS) with Solid Tumors and
Central Nervous System (CNS) Metastases: Integrated Analysis
from 3 Clinical Trials
Tobias Overbeck 1; Salvatore Siena 2, 3; Robert C. Doebele 4; Alice T. Shaw 5;
Christos C. Karapetis 6, 7; Daniel S.W. Tan 8; Byoung Chul Cho 9;
Dong-Wan Kim 10; Myung-Ju Ahn 11; Matthew G. Krebs 12, 13; Koichi Goto 14;
Pilar Garrido 15, 16; Anna F. Farago 5; Herbert H.F. Loong 17; Diego Tosi 18;
Minal Barve 19; Brian P. Simmons 20; Chenglin Ye 20; Xinhui Huang 20;
Alexander Drilon 21
1University of Göttingen, Department of Hematology and Medical Oncology
and Lungentumorzentrum Universität Göttingen, Göttingen
2Grande Ospedale Metropolitano Niguarda, Niguarda Cancer Center, Milan,
Italien
3Università degli Studi di Milano, Department of Oncology and Hemato-
Oncology, Milan, Italien
4University of Colorado, Aurora, CO, United States
5Massachusetts General Hospital Cancer Center, Boston, MA, United States
6Flinders Medical Centre, Adelaide, Australien
7Flinders University, Adelaide, Australien
8National Cancer Centre Singapore, Division of Medical Oncology, Singapore,
Singapore
9Yonsei Cancer Center, Division of Medical Oncology, Seoul, South Korea
10Seoul National University Hospital, Department of Internal Medicine, Seoul,
South Korea
11Samsung Medical Center, Sungkyunkwan University School of Medicine,
Division of Hematology-Oncology, Department of Medicine, Seoul, South Korea
12The University of Manchester, Division of Cancer Sciences, Manchester, United
Kingdom
13The Christie NHS Foundation Trust, Experimental Cancer Medicine Team,
Manchester, United Kingdom
14National Cancer Center Hospital East, Kashiwa, Japan
15Ramón y Cajal University Hospital, Madrid, Spanien
16Universidad Alcalá, Madrid, Spanien
17The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin,
Hong Kong
18Institut du Cancer de Montpellier Inserm U1194, Montpellier University,
Medical Oncology Department, Montpellier, Frankreich
19Mary Crowley Cancer Research Center, Dallas, TX, United States
20Genentech, Inc., South San Francisco, CA, United States
21Memorial Sloan Kettering Cancer Center, Thoracic Oncology Service, Division
of Solid Tumor Oncology, Department of Medicine, New York, NY, United States
Purpose: Entrectinib potently inhibits kinases encoded by the NTRK and
ROS1 genes. It attains therapeutic levels in the CNS with antitumor activ-
ity in intracranial tumor models. We report integrated data (31/05/18 cut-
o) from 3 Phase 1/2 entrectinib trials (ALKA-372-001, EudraCT 2012-
000148-88; STARTRK-1, NCT02097810; STARTRK-2, NCT02568267) in
adults with ROS1 fusion-positive NSCLC (ROS1+) or NTRK fusion-posi-
tive solid tumors (NTRK+), with/without baseline CNS metastases.
Methods: Pts had locally advanced/metastatic NTRK+ or ROS1+ tumors
by nucleic acid-based conrmation. CNS metastases were detected by CT/
MRI. Tumor assessments by blinded independent central review (RECIST
v1.1): wk 4, then every 8 wks. Primary endpoints: objective response rate
(ORR), duration of response (DOR). Secondary endpoints: clinical bene-
t rate (CBR), PFS, OS, intracranial ecacy and safety.
Results: Most pts had ≥1 prior therapy; 33% had baseline CNS metas-
tases. Outcomes for ROS1+ NSCLC (n=53) and NTRK+ solid tumors
(n=54; 24% sarcoma, 18% NSCLC) ecacy evaluable pts by baseline CNS
disease (no v yes) were:
ROS1+ (n=30 v 23):
% ORR (95% CI): 80.0 (61.4, 92.3) v 73.9 (51.6, 89.8)
CR, n (%): 3 (10.0) v 0
PR, n (%): 21 (70.0) v 17 (73.9)
mDOR, mo (95% CI): 24.6 (11.4, 34.8) v 12.6 (6.5, not evaluable [NE])
% CBR (95% CI): 80.0 (61.4, 92.3) v 73.9 (51.6, 89.8)
mPFS, mo (95% CI): 26.3 (15.7, 36.6) v 13.6 (4.5, NE)
mOS, mo (95% CI): NE v NE (10.5, NE)
Intracranial % ORR; mDOR; mPFS: NE v 55.0 (31.5, 76.9; n=20); 12.9
(5.6, NE); 7.7 (3.8, 19.3)
NTRK+ (n=42 v 12):
% ORR: 59.5 (43.3, 74.4) v 50.0 (21.1, 78.9)
CR: 4 (9.5) v 0
PR: 21 (50.0) v 6 (50.0)
mDOR: 12.9 (7.1, NE) v NE (4.2, NE)
% CBR: 61.9 (45.6, 76.4) v 75.0 (42.8, 94.5)
mPFS: 12.0 (8.7, 15.7) v 7.7 (4.7, NE)
mOS: 20.9 (16.8, NE) v 14.3 (51, NE)
Intracranial % ORR; mDOR; mPFS: NE v 54.5 (23.4, 83.3; n=11);
NE (5.0, NE); 14.3 (5.1, NE)
Entrectinib was tolerable with a manageable safety prole; most
treatment-related AEs were grade 1–2.
Conclusions: Entrectinib induced clinically meaningful durable respons-
es in pts with ROS1+ NSCLC or NTRK+ solid tumors with/without CNS
disease.
Conicts of Interest:
Tobias Overbeck: Honoraria (self) from AstraZeneca, BMS, BoehringerIngelheim,
Eli Lilly, Medac, MSD, Novartis, Roche/Genentech; Advisory/Consultancy for
AstraZeneca, BMS, BoehringerIngelheim, Eli Lilly, Medac, MSD, Novartis,
Roche/Genentech; Research grant/Funding (institution) from AstraZeneca, Eli
Lilly, Roche/Genentech, Sano-Aventis; Travel/Accommodation/Expenses from
AstraZeneca, Boehringer-Ingelheim, Eli Lilly, and Roche/Genentech.
Salvatore Siena: Advisory board member for Amgen, Bayer, BMS, CheckmAb,
Celgene, Clovis, Daiichi-Sankyo, Incyte, Merck, Novartis, Roche/Genentech, and
Seattle Genetics.
Robert C. Doebele: Honoraria from Genentech/Roche, Takeda/Millenium; Advi-
sory board for Genentech/Roche, Rain erapeutics; Travel reimbursement from
Genentech/Roche, Ignyta; Licensing fees for biological materials from Genentech/
Roche, Ignyta, Foundation Medicine, Loxo Oncology; Consulting for Ignyta, Loxo
Oncology, Bayer, Rain erapeutics; Sponsored research for Ignyta, Loxo Oncol-
ogy; Stock ownership at Rain erapeutics; Licensing fees from patent from Rain
erapeutics, and Abbott Molecular.
Alice T. Shaw: Consulting, honoraria, and institutional (research) support from
Genentech, Roche, and Ignyta.
Christos C. Karapetis: Advisory board role for Roche, MSD, BMS, Amgen, Astra-
Zeneca, Eisai; Honoraria from Roche, Eisai, and AstraZeneca.
Daniel S.W. Tan: Honararia (self) from Merck, Pzer, Novartis, Boehringer
Ingelheim, Roche, Takeda; Advisory / Consultancy for Novartis, Bayer, Boeh-
ringer Ingelheim, Celgene, Astra Zeneca, Eli-lily, Loxo; Research grant / Funding
(self) from Novartis, Astra Zeneca, GlaxoSmithKline, Bayer, Pzer; Travel /
Accommodations / Expenses from Merck, Pzer, Novartis, Boehringer Ingelheim,
Roche,Takeda.
Byoung Chul Cho: Research funding from Novartis, Bayer, AstraZeneca,
MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono
Pharmaceuticals, Dizal Pharma, MSD; Consulting role for Novartis, AstraZeneca,
BoehringerIngelheim, Roche, Bms, Ono Pharmaceuticals, Yuhan, Pzer, Eli Lilly,
Janssen, Takeda, MSD; Stock ownership at eraCanVac Inc., Gencurix, Inc.,
Bridge Biotherapeutics; Royalty from Champions Oncology.
Dong-Wan Kim: Research funding (institution) from Alpha Biopharma, Astra-
Zeneca/MedImmune, Hanmi, Janssen, Merus, Mirati erapeutics,Inc, MSD,
Novartis, Ono Pharmaceutical, Pzer, Roche/Genentech, Takeda, TP erapeutics,
Xcovery, and Yuhan.
Myung-Ju Ahn: Advisory / Consultancy for AstraZencea, Lilly, MSD, Takeda,
Alpha pharmaceuticals, Roche, Yuhan.
Matthew G. Krebs: Advisory Boards for Roche, Janssen, OCTIMET Oncology,
Achilles erapeutics; Travel grants from AstraZeneca, BerGenBio; Research fund-
ing from Roche.
Koichi Goto: Honoraria (institution) from MSD, AstraZeneca, Novartis Pharma,
LifeTechnologies Japan, Pzer Japan Inc., Bristol-Myers Squibb., Ono Pharma-
ceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd,
Eli Lilly Japan, Nippon Boehringer lngelheim Co., Ltd, Takeda Pharmaceutical
Co., Ltd, Otsuka Pharmaceutical, Kyowa Hakko Kirin Co.,Ltd; Research grant/
Funding (institution) from Taiho Pharmaceutical Co., Ltd, Chugai Pharmaceuti-
cal Co., Ltd, Ono Pharmaceutical Co., Ltd, Astra Zeneka, Sumitomo Dainippon
Pharma Co., Ltd, Bristol-Myers Squibb, MSD, Astellas Pharma Inc., Eisai Co., Ltd,
DAIICHI SANKYO Co., Ltd, Pzer Inc., Kyowa Hakko Kirin Co., Ltd, Novartis
Pharma, Takeda Pharmaceutical Co., Ltd, Eli Lilly Japan, Merck Serono Co., Ltd,
Ignyta,Inc., Boehringer Ingelheim Japan, Inc., Janssen Pharmaceutical, Ignyta,
Inc., Loxo Oncology, Sysmex Corporation Xcoo, Inc., and Medical & Biological
Laboratories Co., Ltd.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 35
Inhalt
2018
Index
2018
Pilar Garrido: Consulting and advisory services (self) for Roche, MSD, BMS,
Boehringer Ingelheim, Pzer, AbbVie, Guardant Health, Novartis, Eli Lilly,
AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaking, public pre-
sentations (self) from Takeda, AstraZeneca, Roche, MSD, BMS, Pzer, Novartis,
Boehringer Ingelheim, Gilead Sciences, Rovi; Financial support for clinical trials
(institution) from Roche, MSD, BMS, Takeda, Eli Lilly, Pzer, Novartis, Phar-
mamar, Celgene, Sano, Gsk, eradex Oncology, Blueprint Medicines; Financial
support for contracted research (institution) from Guardant Health, and Sysmex.
Anna F. Farago: Advisory/Consultancy for Roche, Genentech, Loxo Oncology,
Bayer, Pharmamar, AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingel-
heim; Research grant/Funding (self) from AbbVie, AstraZeneca; Research grant/
Funding (institution) from AbbVie, and AstraZeneca, Pharmamar, Merck, Bris-
tol-Myers Squibb, Amgen, Genentech/Roche, Ignyta, Loxo, Bayer, Novartis; Travel/
Accommodation/Expenses from Roche, Genentech, Loxo, Bayer, Pharmamar,
AstraZeneca, Bristol-Myers Squibb, AbbVie, and Boehringer Ingelheim.
Herbert H.F. Loong: Consulting or advisory role (self) for GlaxoSmithKline,
Roche/Genentech, Novartis; Speakers’ Bureau (self) for AbbVie, Ignyta, Novartis;
Research Funding (institution) from MSD Oncology; Travel/Accommodation/
Expenses from Roche, MSD Oncology, Bayer, and Pzer.
Diego Tosi: Travel expenses for scientic meetings from Pzer, Astellas, MSD;
Research funding from Janssen, Astellas, Ipsen; Research contract from Phosplatin
erapeutics; Research grant from Ipsen.
Minal Barve: No conicts of interest to disclose.
Brian P. Simmons: Employment at Genentech, Inc.; Stock ownership at Roche.
Chenglin Ye: Employment at Genentech, Inc.; Stock ownership at Roche.
Xinhui Huang: Employment at Genentech, Inc.; Stock ownership at Roche.
Alexander Drilon: Honoraria or advisory boards for Ignyta/Genentech/Roche,
Loxo/Bayer/Eli Lilly, Takeda/Ariad/Millenium, TP erapeutics, AstraZeneca,
Pzer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui erapeu-
tics, Exelixis, Tyra Biosciences, VerastemOncology, MORE Health, AbbVie;
Associated research paid to institution: Pzer, Exelixis, GlaxoSmithKline, Teva
Pharmaceutical Industries, Taiho Pharmaceutical Co., Ltd, Pharmamar; Research
for Foundation Medicine; Royalties from Wolters Kluwer; Food and beverage from
Merck, Puma; CME Honoraria from Medscape, OncLive, PeerVoice, Physicians’
Education Resources, Targeted Oncology, Research to Practice, Oncology.
All authors: Medical writing and editorial support for the original abstract was
provided by Gardiner-Caldwell Communications, Asheld Healthcare Commu-
nications and sponsored by Roche in accordance with Good Publication Practice
guidelines. Support for third-party editing assistance for this abstract, furnished
by Helen Singleton, PhD, Sammi Cham, BA, and Niamh Gould, BA, of Health
Interactions, was provided by Roche Pharma AG. is study was funded by
F. Homann La-Roche, Basel, Switzerland.
407
Regorafenib in Advanced High Grade Glioma
Irina Gepfner-Tuma 1, 2; Theophilos Tzaridis 3, 4; Ulrich Herrlinger 3;
Ghazaleh Tabatabai 1, 2
1Interdisciplinary Division of Neurooncology, Hertie-Institute for Clinical Brain
Research, Tuebingen, Deutschland
2Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart,
University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,
Tuebingen, Deutschland
3Division of Neuro-Oncology, Department of Neurology and Center of
Integrated Oncology, University Hospital Bonn, Bonn, Deutschland
4Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital
Bonn, Bonn, Deutschland
Purpose: e REGOMA phase II trial has recently reported an overall
survival benet of the oral multikinase inhibitor regorafenib in progres-
sive glioblastoma1. We analyzed retrospectively the clinical ecacy of re-
gorafenib and treatment-related adverse events in a series of patients with
advanced stages of glioma.
Methods: Patients with progressive glioma received 80-160 mg rego-
rafenib daily (3 weeks on, 1 week o) until tumor progression or dose-lim-
iting toxicity.
Results: We treated 24 patients with regorafenib (21 glioblastoma, 1 as-
trocytoma, 1 midline glioma, 1 oligodendroglioma). Median progres-
sion-free survival was 2.1 months, median overall survival 4.1 months.
e occurrence of hand-foot-syndrome correlated with longer median
survival. Adverse events of CTCAE grades 1-3 included fatigue (13/24,
54%), dermatological toxicity (8/24, 33%), increased lipase (5/24, 21%)
and endocrinological events (4/24, 17%). One patient developed a treat-
able corticosteroid-responsive aseptic meningitis during regorafenib.
Conclusions: In the absence of further available treatment strategies, re-
gorafenib could be evaluated as an option in progressive glioblastoma2.
Dermatological toxicity might be useful as a clinical marker for patient
stratication and could be investigated in future prospective trials. Given
the broad application of regorafenib beyond the eld of neuro-oncology,
the occurrence of a treatable aseptic meningitis3 might be of interest for
the general clinical management during regorafenib treatment.
References:
1. Lombardi et al., Lancet Oncol 2019
2. Tzaridis et al., Neuro Oncol 2019
3. Gepfner-Tuma et al., Neuro Oncol Practice 2019
Disclosure Statement: IG-T: speaker’s fees from Novocure; grant from Medac.
UH: grants and personal fees from Roche; personal fees and nonnancial support
from Medac; personal fees from Novocure; Novartis; Daichi Sankyo; Riemser;
Noxxon; Abbvie; Bayer. GT served on Advisory Boards of BMS; MSD; AbbVie;
received research and/or travel grants from Roche; Novocure; Medac; speaker’s
fees from Medac; Novocure.
438
TargetingofCSF1R and PD1 in Experimental Glioma
Justyna M. Przystal 1, 2, 3; Hannes Becker 1, 3; Denis Canjuga 1; Carola H. Ries 4;
Martina Schmittnaegel 4; Nataliya Korinetska 1; Marilin Koch 1;
Jens Schittenhelm 2, 3, 5; Marcos Tatagiba 1, 3; Susanne C. Beck 1;
Ghazaleh Tabatabai 1, 2, 3
1Hertie Institute for Clinical Brain Research, Interdisciplinary Division of Neuro-
Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen,
Tübingen, Deutschland
2German Translational Cancer Consortium (DKTK), DKFZ partner site Tübingen,
Tübingen, Deutschland
3Comprehensive Cancer Center Tübingen-Stuttgart, Center for Neuro-Oncology,
University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen,
Deutschland
4Roche Innovation Center Munich, Oncology Division, Roche Pharmaceutical
Research and Early Development, Penzberg, Deutschland
5Institute for Neuropathology, University Hospital Tübingen, Tübingen,
Deutschland
Purpose: Glioblastoma is an aggressive primary tumor of the central ner-
vous system. e median overall survival of patients is in the range of 1.5
years even in selected clinical trial populations investigating multimodal
therapies. Novel therapeutic strategies are urgently needed. erapeutic
targeting of the glioblastoma-associated microenvironment is a promis-
ing approach in this regard. Particularly macrophages represent a highly
abundant population of tumor-inltrating host cells. e colony stimulat-
ing factor-1/colony stimulating factor-1 receptor (CSF1/CSF1R) axis plays
an important role for macrophage dierentiation and survival.
Methods: To assess CSF1R in human glioblastoma, we performed CSF1R
staining in human tissue samples from primary and recurrent glioblasto-
ma. For targeting the tumor microenvironment (TME) we performed an
anti-CSF1R approach in experimental glioma using the antibody clone
2G21 syngeneic preclinical glioma mouse models. TME-associated treat-
ment patterns were evaluated by histology and immunochemistry.
Results: CSF1R is present in human samples of primary and recurrent
glioblastoma. Monotherapy with anti-CSF1R antibody increased latency
until the onset of neurological symptoms in SMA560-bearing VM/Dk
mice and CD204 and CD11b positive cells were reduced suggestive aer
treatment. A combination of anti-PD1 and anti-CSF1R antibodies further
prolonged the symptom-free survival and led to higher CD8+/CD4+ ratios
in vivo.
Conclusions: Our results identify CSF1R as a promising therapeutic tar-
get for glioblastoma, probably in combination with PD1 inhibition.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts36
Inhalt
2018
Index
2018
Reference:
1. Ries, C. H., et al. (2014). “Targeting tumor-associated macrophages with
anti-CSF-1R antibody reveals a strategy for cancer therapy.” Cancer Cell 25(6):
846-859
Disclosure Statement: HB received funds from a Siegmund Kiener doctoral
fellowship. GT received grants from Roche Diagnostics. GT received research
and/or travel grants from Roche, Novocure, Medac; speakers` fees from Medac,
Novocure.
454
Argyrin F Leads to Targetable Treatment-Induced
Vulnerabilities in Experimental Glioma
Bianca Walter 1; Denis Canjuga 1; Michael Ghosh 2; Susanne C. Beck 1;
Przemyslaw Bozko 3; Stefan Stevanovic 2; Nisar Malek 3;
Ghazaleh Tabatabai 1
1Hertie Institute for Clinical Brain Research , Interdisciplinary Division of Neuro-
Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen,
Tübingen, Deutschland
2Interfaculty Institute for Cell Biology, Department of Immunology, University of
Tübingen, Tübingen, Deutschland
3Department of Internal Medicine I, University Hospital Tübingen, Eberhard
Karls University Tübingen, Tübingen, Deutschland
Purpose: Glioblastoma is an aggressive primary tumor of the nervous
system with limited ecient treatment options. e proteasome inhibi-
tor Argyrin A and its recently developed analogue Argyrin F display an-
ti-tumor activity [1, 2]. Proteasome inhibition is a promising therapeutic
strategy in glioma. In fact, the EORTC 1709 trial investigates Marizomib
in newly diagnosed glioblastoma. We consequently aimed at exploring the
anti-glioma activity of Argyrin F in experimental glioma to evaluate its
suitability for further clinical development in glioblastoma.
Methods: We performed an in-depth characterization of Argyrin F in-
duced eects in LN229, LNZ308, SMA560, and GL261 cell lines by acute
cytotoxicity (24 h and 48 h) and clonogenicity assays. We determined
p27KIP1 levels by immunoblot, proteasome activity by uorometry, and cell
cycle progression by ow cytometry. We investigated the HLA ligandome
with an EC20 dosage and conducted in vivo treatments in the syngeneic
SMA560/VMDk glioma model.
Results: We observed treatment-related reductions of proteasome activi-
ty, cell viability and clonogenic survival (> 50% reduction at 0.5 mg/mL)
and an increase of p27KIP1 levels. Argyrin F induces the presentation of im-
munogenic peptides on the cell surface. In vivo analysis and histological
characterizations are ongoing and will be presented.
Conclusions: Argyrin F has anti-glioma activity and might, therefore, be
an interesting therapeutic approach for clinical translation in glioblasto-
ma, potentially in combination with immunotherapeutic strategies.
References:
1. Chen X et al, Cancer letters 2017
2. Nickeleit I et al, Cancer Cell 2008
Disclosure Statement: GT served on Advisory Boards of BMS; MSD and AbbVie;
received research and/or travel grants from Roche Diagnostics; Novocure and
Medac; received speaker’s fees from Medac; Novocure.
492
The Inuence of an Infection with S. Aureus on Growth and
Cytokine Secretion of Glioblastoma Multiforme (GBM)
Claudia Lemke 1; Susanne Grube 1; Lorena Tuchscherr 2; Rolf Kal 1;
Jan Walter 1, 3
1Klinik für Neurochirurgie, Universitätsklinikum Jena, Jena, Deutschland
2Institut für Medizinische Mikrobiologie, Universitätsklinikum Jena, Jena,
Deutschland
3Klinik für Neurochirurgie, Klinikum Saarbrücken, Saarbrücken, Deutschland
Purpose: e relationship between postoperative infections and a pro-
longed survival in patients with GBM remains controversial. Neverthe-
less, there are no studies on the inuence of infections of GBM cells on
survival and proliferation of these cells. ere is evidence to suggest that
pathogens may stimulate the tumor cells to secret cytokines. To test these
hypotheses, we established an in vitro infection model with Staphylococ-
cus aureus.
Methods: Four primary GBM cultures and one culture of human brain
astrocytes (HBA) were infected with the strain 6850 of S. aureus and ob-
served for 7 days. At dierent timepoints the number of intracellular bac-
teria was determined. A gene expression analysis was performed by qPCR
and the secretion of proinammatory cytokines (IL6, IL8) was measured
by ELISA.
Results: All cell cultures expressed factors to enable bacterial internal-
ization and were infectable with S. aureus. e GBM cells ingested up
to 4.7% of the bacteria, the HBA up to 0.3%. e HBA eliminated the
bacteria very quickly and survived better than the GBM, but also the
GBM showed a quick elimination and recovered. ere was a signi-
cant increase (p<0.01) in expression of the proliferation markers MKI67
(6.7fold), PLK1 (2.9fold) and the transcription factor c-Jun (3.0fold) in
all infected GBM cells, compared to uninfected cells. 24h aer infection,
there was an increase in secretion of the proinammatory cytokines IL6
(7.2fold, p<0.001) and IL8 (1.8fold) in the GBM cells, compared to unin-
fected cells. e HBA also showed an increase in IL6 and IL8 secretion,
but to a lower extent (IL6: 5.6fold, IL8: 1.1fold). Interestingly, the unin-
fected HBA showed a signicantly higher IL6 (up to 10.2fold) secretion
than the uninfected GBM cells.
Conclusions: In summary, both GBM and HBA could be infected by S.
aureus, whereby the GBM proved to be more vulnerable to the infection.
Furthermore, there was an increased secretion of proinammatory cyto-
kines in GBM, comparable to uninfected HBA, indicating a stimulation
of the GBM cells.
Disclosure Statement: ere are no conicts of interest.
506
Radiotherapy for Glioblastoma – Feasibility, Results and
Correlation of Target Volumes and Location of Relapse in a
Monoinstitutional Sample
Christoph Süß 1; Rüdiger Schenk 2; Felix Steger 1; Elisabeth Bumes 3;
Oliver Kölbl 1; Matthias Hautmann 1
1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,
Regensburg
2Klinik für Innere Medizin, St. Elisabeth-Krankenhaus, Essen
3Klinik und Poliklinik für Neurologie der Universität Regensburg,
Bezirksklinikum Regensburg, Regensburg
Purpose: Glioblastoma is the most common primary brain tumor. Radio-
therapy is a well-established adjuvant treatment modality. However, near-
ly all patients suer from a relapse of the tumor. e aim of this survey was
to document the feasibility and results and to correlate the location of the
relapse with the target volumes and isodoses.
Methods: All patients, which received RT or RCT at the University Hospi-
tal Regensburg for glioblastoma from 2004 to 2012 were included.
94 patients could be identied. e median age was 57 years with 60.6%
male and 39.4% female patients. For 30 patients we could perform a fu-
sion of the MRI scan showing the relapse with the treatment plans and
correlate the localization.
e median follow-up was 16 months (IQR 9 to 24 months).
Results: e feasibility of radiotherapy was good.
e median overall survival was 14 months. Aer 12 months 62% and
aer 24 months 20% of the patients were alive.
e median progression free survival was 8 months. Aer 6 months 40%,
aer 12 months 75% and aer 24 months 93% suered from a tumor
relapse.
In most of the cases the main volume of the recurrent tumor occurred
within the initial high dose area (60 Gy). Only one recurrent glioblastoma
was completely outside the initial target volumes.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 37
Inhalt
2018
Index
2018
Conclusions: e feasibility of radiotherapy was good, but the survival
data are still unsatisfying. e main challenge is the avoidance of local
relapse inside the target volumes.
Disclosure Statement: On behalf of all authors, the corresponding author declares
that there are no conicts of interest.
514
Inhibiting BHLH Transcriptional Networks Using Dominant
Negative E47 Leads to a Strong Anti-Glioma Activity in Vitro
and in Vivo
Marilin Koch 1, 2; Stefan Czemmel 3; Felix Lennartz 2, 4; Sarah Beyeler 1, 2;
Justyna Pryztal 1, 2; Parameswari Govindarajan 1, 2; Denis Canjuga 1, 2;
Manfred Neumann 1, 2; Patrizia Rizzu 5; Marcos Tatagiba 6; S Rajaraman1, 2;
Sven Nahnsen 3; Peter Heutink 5; Olivier Raineteau 7; Ghazaleh Tabatabai 2, 4
1Interdisziplinäre Sektion Neuroonkologie, Klinik und Poliklinik für Neurologie,
Universitätsklinikum Tübingen, Eberhard-Karls-Universität Tübingen, Tübingen,
Deutschland
2Hertie-Institut für klinische Hirnforschung, Tübingen, Deutschland
3Zentrum für Quantitative Biologie (QBiC), Eberhard-Karls-Universität Tübingen,
Tübingen, Deutschland
4Interdisziplinäre Sektion Neuroonkologie, Klinik und Poliklinik für Neurologie,
Klinik für Neurochirurgie, Universitätsklinikum Tübingen, Eberhard-Karls-
Universität Tübingen, Tübingen, Deutschland
5Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen,
Deutschland
6Interdisziplinäre Sektion Neuroonkologie, Klinik für Neurochirurgie,
Universitätsklinikum Tübingen, Eberhard-Karls-Universität Tübingen, Tübingen,
Deutschland
7Inserm, Stem Cell and Brain Research Institute, Université de Lyon, Bron,
Frankreich
Inhibiting bHLH transcriptional networks using dominant negative
E47 leads to a strong anti-glioma activity in vitro and in vivo
Purpose: e transcription factor E47 forms heterodimers with he-
lix-loop-helix (HLH)/basic helix-loop-helix (bHLH) proteins such as
ID-1 and Olig2, both of which are frequently overexpressed in gliomas.
e dominant negative variant of E47 (dnE47) lacks a nuclear transloca-
tion signal and eventually leads to sequestration of HLH and bHLH fac-
tors into the cytoplasm. In this study, we investigated a combination of
this approach with standard of care (SOC) temozolomide and irradiation
to explore its therapeutic ecacy and molecular mechanisms.
Methods: Doxycycline-inducible dnE47 lentivirus was used to transduce
long-term and stem cell glioma cell lines. In vitro experiments including
immunoblots, immunocytochemistry stainings, cytotoxicity and clono-
genic assays were performed for functional evaluation of the dnE47 ap-
proach. Eects upon latency of symptom onset were investigated in vivo.
CAGE and RNA-seq were used to study transcriptional changes upon
dnE47 induction.
Results: dnE47 induction led to cytoplasmatic sequestration of HLH/
bHLH proteins, reduced proliferation, increased cytotoxicity and reduced
clonogenic survival in vitro. In vivo experiments showed a longer latency
for symptom onset. CAGE and RNA-seq analysis pointed to alterations in
several cancer-related pathways.
Conclusions: dnE47-mediated inhibition of HLH/bHLH networks in-
duced actionable molecular alterations in glioma that could be exploited
to develop novel therapies.
Disclosure Statement: MK received funds from Elfriede Kröner Stiung, GT
served on Advisory Boards of BMS, MSD and AbbVie; received research and/or
travel grants from Roche Diagnostics, Novocure and Medac; received speaker’s
fees from Medac, Novocure
584
Pretreatment with the mTOR Inhibitor Everolimus Enhances
Glioblastoma Sensitivity to Temozolomide in Vitro
Aaron Lawson McLean; Diana Freitag; Rolf Kal; Jan Walter
Klinik für Neurochirurgie, Universitätsklinikum Jena, Jena, Deutschland
Purpose: Glioblastoma (GBM) is the most invasive and devastating pri-
mary brain tumor with a median overall survival time of 18 months de-
spite aggressive multimodal therapy. New therapeutic strategies, poten-
tially involving multistage chemotherapy regimens, are needed to enhance
survival. is applies not only in the setting of progressive disease but also
in frontline protocols.
Methods: Four distinct primary GBM cell cultures were treated with the
mTOR inhibitor everolimus and/or the tyrosine kinase inhibitor axitinib.
Untreated cell cultures and cultures treated with the corresponding vehicle
(ethanol and/or DMSO) acted as controls. Treatment was applied to each
culture once and the IC10, IC25 and IC50 concentrations previously
determined by MTT assay were used. Surviving cells were cultured for
three passages and then tested for chemosensitivity to lomustine and
temozolomide.
Results: Cells resistant to the initial treatment could be cultivated in all
study groups. However, cells treated with the combination of everolimus
and axitinib, and with axitinib alone (IC25 and IC50), showed the stron-
gest treatment eects. Cells in these groups no longer adhered to the sub-
strate of culture vessels aer two passages. Cells that could be cultured
showed no signicant dierence in chemosensitivity to lomustine aer
pretreatment. However, cells treated with everolimus were signicantly
more sensitive to temozolomide. Vehicle pretreatment was also associated
with a trend towards increased temozolomide sensitivity.
Conclusions: Everolimus pretreatment strongly enhances GBM cell che-
mosensitivity to temozolomide. is nding may have relevance for GBM
treatment strategies and should now be explored in vivo.
Disclosure Statement: e authors report no conicts of interest.
655
Analysis of Possible Inuence of Cortex Temperature
on Patient Cognition during Awake-Surgery
Johannes Knipps; Marcel Alexander Kamp; Marion Rapp;
Hans-Jakob Steiger; Daniel Hänggi; Michael Sabel
Klinik für Neurochirurgie, Uniklinik Düsseldorf, Düsseldorf, Deutschland
Purpose: During skull trepanning, it is possible to observe an intraop-
erative heat loss at the brain surface due to convection as well as thermal
radiation. is eect is intensied involuntarily, when rinsing uid adapts
to room temperature during surgery, or intentionally, when cerebral sei-
zures are stopped by active ice-water rinsing. However, the patient’s active
cognitive cooperation is essential, especially during awake phase. e aim
of this pilot study is to investigate the inuence of cortex temperature on
cognition during awake-surgery.
Methods: During an awake-surgery, the complete course of the cortexs
temperature was analysed continuously by an imaging camera. is was
performed with 8 patients at a total of 52 measuring points. e body’s
core and the cortical temperature changes were determined over time –
split into phases where no water, warm ush (36°C) or ice water was used.
As a surrogate for the cognitive performance of patients, a reaction time
test was performed intraoperatively on the patient.
Results: During the rst measurement the cortex’s temperature was
37.1°C (36.2-37.5°C). e cortex’s surface temperature approached room
temperature (median: 26.2°C) without proper regular irrigation (mean -
1.1°C in the rst 10 min, mean - 2.4°C in the rst 15 min).
Average reaction time was 742 milliseconds. At the same time, average
reaction time at a cortex temperature < 35°C was 1421 milliseconds, at a
cortex temperature 35°C 572 milliseconds (p < 0.05). At a cortex tempera-
ture < 35°C, reaction time improved again aer rinsing with warm liquid.
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Conclusions: Our pilot study suggests a continuous drop in the cerebral
cortex’s temperature during (awake) phase of surgery. Furthermore; the
average reaction time correlated with the temperature of the cortex sig-
nicantly. e brains temperature may have signicant impact on the
cognitive performance of patients during the awake phase. is possible
connection should be investigated in further studies.
658
Evaluation of MRI-Artefacts After Removal of Cerebral
Applied Iron Oxide Particles in a Sheep Brain Model
Johannes Knipps; Marcel Alexander Kamp; Marion Rapp;
Jan Frederick Cornelius; Hans-Jakob Steiger; Daniel Hänggi;
Michael Sabel
Klinik für Neurochirurgie, Uniklinik Düsseldorf, Düsseldorf, Deutschland
Purpose: A possible adjuvant therapy method for patients with recurrent
glioblastoma multiforme is the intra-tumoral application of magnetic iron
oxide particles and the excitation of these particles by an alternating mag-
netic eld. By using this method cancer-killing mechanism should be in-
duced. An obvious problem is the fact that further MRI follow-up checks
are no longer possible aer insertion of metal into the skull because of
artefacts. Our study’s aim is to evaluate the possibility of post-interven-
tional removal of iron oxide particles ex-vivo that would allow subsequent
morphological imaging.
Methods: A precisely dened amount of iron oxide particles (applied via
carrier material) was injected into ex-vivo sheep brains. Subsequently,
brains were heated to 45°C in water for 30 minutes, approaching heat-gen-
erating activation mechanism and demonstrated on the MRI. Subse-
quently, the particles (1) were removed by rinsing (0.9% NaCl) and (2) by
means of ultrasonic aspirator. In a third group, only the carrier material
was removed. e completeness of the iron oxide particles’ removal was
quantied on the MRI.
Results: e experiments were performed on a total of three sheep brains.
When particles were enclosed, pronounced artefacts were found on the
MRI. Aer removal via extensive irrigation or usage of an ultrasound
aspirator, the MRI could no longer detect any iron oxide induced arte-
facts. By selective removal of the carrier material, pronounced artefacts
remained aerwards.
Conclusions: A complete removal of iron oxide particles ex-vivo allowing
an artefact-free MRI imaging seems to be possible. Further studies must
show whether this is possible in-vivo.
660
Comparison of the Cerebral Thermal Ambient Temperature
During the Use of Conventional Coagulation Forceps and
Coagulation Forceps with Active Heat Conduction
Johannes Knipps; Marcel Alexander Kamp; Marion Rapp;
Jan Frederick Cornelius; Hans-Jakob Steiger; Daniel Hänggi;
Michael Sabel
Klinik für Neurochirurgie, Uniklinik Düsseldorf, Düsseldorf, Deutschland
Purpose: Bipolar coagulation forceps are currently used as standard
during (neuro-) surgical operations. Principle of the forceps is based on
heat production that eects a thermally induced tissue coagulation. At the
same time, a heat-related environmental reaction occurs, which can also
be accompanied by damage to the surrounding physiological tissue. e
aim of our study is to compare ambient temperatures aer coagulation
with conventional coagulation forceps and coagulation forceps with active
heat conduction.
Methods: We used an ex-vivo sheep brain model developed at our labo-
ratory: for this purpose, an area of sheep brains encompassing 4mm2 was
coagulated ex-vivo (with a surface temperature of 28°C), within a xed
time of 5 seconds, using 1.) conventional coagulation forceps (Bipolar)
and 2.) coagulation forceps with active heat conduction (Iso). roughout
the process, the temperature of the coagulation area and surrounding tis-
sue was documented by means of a thermal imaging camera during and
aer coagulation, being subsequently evaluated electronically.
Results: e experiments were carried out on a total of four sheep brains.
We were able to show that during the use of conventional coagulation
forceps temperatures above the previously measured surface temperature
could still be measured several centimetres away from the coagulation
area (mean Tmax: 86.75°C, ambient reaction 1cm: 42.8°C). Compared to
that result, the rise of the ambient temperature was signicantly lower
when coagulation forceps with active heat conduction were used (mean
Tmax: 46.9°C), ambient reaction 1cm: mean 34.0°C.
Conclusions: Our thermography measurements have proven that even
several centimetres away from the actual coagulation area, increased and
thus potentially harmful temperatures can be found and shown on the tis-
sue. Since heat has a toxic eect on brain tissue; the application and inten-
sity of coagulation forceps should be used carefully. More recent surgical
instruments with active heat conduction seem to be helpful in reducing
collateral damage due to heat exposure.
Developmental Therapeutics: Cytotoxic Chemotherapy
Poster
848
High Throughput Drug Screening on Pleural Eusion for
Optimizing Cytotoxic Treatment in Metastatic Breast Cancer
Peter Ugocsai 1; Christian Werno 2; Valeria Gerthofer 1; Kathrin Weidele 2;
Natasa Stojanovic 2; Ste Treitschke 2; Kamran Honarnejad 2;
Christoph Andreas Klein 3; Olaf Ortmann 1; Stephan Seitz 1
1Department of Gynecology and Obstetrics, University Medical Center
Regensburg, Regensburg, Deutschland
2Fraunhofer-Institute for Toxicology and Experimental Medicine, Regensburg,
Deutschland
3Department of Experimental Medicine and Therapy Research,University
Medical Center Regensburg, Regensburg, Deutschland
Purpose: Finding the optimal beyond 2nd line therapeutic strategy in met-
astatic breast cancer (mBC) is challenging. Ex vivo drug tests on patient´s
cancer cells may help to identify eective substances, however despite of a
good correlation between ex vivo test results and in vivo therapy response,
the required time for drug testing (cell isolation, expansion and drug re-
sponse test) is far beyond the possibilities of clinical utilization, in combi-
nation with a low number of candidate drugs tested. We introduce here a
novel approach for ex vivo high throughput drug screening on malignant
pleural eusion to identify substances for an eective beyond 2nd line cy-
totoxic treatment.
Methods: For an optimal analysis of in vitro drug response a suspension of
single cells with high number of tumor cells is required. Malignant pleu-
ral eusion of 5 mBC patients was analyzed for eligibility. Drug response
assays using a drug library of 133 agents were tested at 5 concentrations in
duplicates using an in vitro viability assay for reproducibility and correla-
tion to the retrospective clinical course of the patients.
Results: Malignant cell count in the analyzed pleural eusions (>200ml)
was sucient in all cases to generate a standardized single cell suspension
for drug testing. Drug response assays were successfully carried out in all
5 cases, providing results within 96 hours aer pleural puncture. e in
vitro reproducibility was 100% in repeated tests. We also detected a 100%
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2018
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2018
correlation between the in vitro test results of non-responding drugs and
retrospective clinical progress under the corresponding cytotoxic agent.
Conclusions: High throughput drug response screens can be successfully
carried out on pleural eusion within 4 days. e high number of cytotox-
ic agents and the rapid testing allow the identication of drug candidates
for beyond 2nd line treatment in rapidly progressing mBC. Further investi-
gations are required for the assessment of the prospective prognostic val-
ue. e need for pleural eusion is also a current limitation.
Disclosure Statement: no conict of interest
Developmental Therapeutics: Immunotherapy/Cellular Therapy
Best-of-Abstracts-Vorträge
467
CAR-T Cells Directed Against B Cell Surface Antigens for the
Targeting of B Cell Non-Hodgkin’s Lymphoma
Mario Bunse 1; Janina Pfeilschifter 1; Julia Bluhm 1; Wolfgang Uckert 1;
Jörg Westermann 2; Armin Rehm 1; Maria Zschummel 1; Uta Höpken 1
1Berlin, Max-Delbrück-Center for Molecular Medicine, Berlin, Deutschland
2Berlin, Charite-University Medicine, Berlin, Deutschland
Purpose: Chimeric antigen receptor (CAR)-T cell therapy is a new type
of cellular immunotherapy that is based on the adoptive transfer of au-
tologous T cells genetically modied with an engineered immunoglob-
ulin-derived receptor that recognizes tumor-associated antigens. CAR-T
cell therapies targeted at the CD19 antigen on leukemia and lymphoma
B cells showed substantial clinical ecacy, currently, more than 40 CD19
CAR-T cell studies are registered at the FDA for the treatment of B-NHL
and B-ALL. However, anti-CD19 CAR-T cell therapy can become inef-
fective due to CD19 antigen loss. is signies the development of im-
munotherapies for additional tumor-associated targets, either for salvage
therapy, or as an alternative to anti-CD19 CARs.
Methods and Results: Here, we identied a B cell homing receptor as an
alternative target for CAR-T cell immunotherapy of mature B cell lym-
phomas by demonstrating strong surface expression of CXCR5 on B-NHL
cell lines but also on primary tumor samples. Based on an anti-human
CXCR5 antibody, we designed a humanized scFv that was incorporat-
ed into a second-generation CAR backbone to generate the anti-human
CXCR5 CAR. e CXCR5 CAR endows T cells with high avidity, neces-
sary for anti-tumor ecacy on lymphoma cell lines, and on primary pa-
tient-derived B-NHL cells. Also, the CXCR5 CAR confers T cell-reactivity
against benign mature B cells, and concomitantly reacts towards lympho-
ma-supportive T cells. No unwanted T cell-reactivity against myeloid
cells and various non-hematopoetic cells from human tissues were ob-
served. A syngeneic mouse model of anti-CXCR5 CAR-T cell therapy was
used to further prove absence of unexpected on-target/o-tumor eects
in-vivo. Finally, CXCR5 CAR-T cells exhibit a robust in-vivo antitumor
activity in a mouse xenogra model ofhuman B-NHL.
Conclusions: We propose CXCR5-targeted CAR-T cells as an attractive
alternative treatment strategy for B-NHL through combined elimination
of lymphoma and tumor-supporting T cells.
Disclosure Statement: All authors declare that they have no competing interests.
Vorträge
819
Feasibility of Autologous Lymphocyte Apheresis in Heavily-
Pretreated Patients Intended to Undergo Therapy with
Chimeric Antigen Receptor (CAR)-T Cells
Vladan Vucinic 1, 1; Saskia Hell 1; David Beverungen 1; Enrica Bach 1;
Sabine Leiblein 1; Michael Cross 1; Madlen Jentzsch 1; Yvonne Remane 2;
Andrea Hille 1; Sandra Otto 1; Elena Ruschpler 1; Uwe Platzbecker 1
1Universitätsklinikum Leipzig AöR, Medizinische Klinik I, Leipzig, Deutschland
2Universitätsklinikum Leipzig AöR, Apotheke, Leipzig, Deutschland
Purpose: One of the essential steps in manufacturing CAR-T cells is the
apheresis of autologous CD3+ lymphocytes. However, due to previous cy-
totoxic therapy, lymphopenia or disease status it is not always possible to
perform a sucient collection. Here we evaluated the feasibility of collect-
ing adequate apheresis products.
Results: Between February and August 2019, we performed 15 collec-
tions in 12 patients with relapse/refractory diuse large B cell Lymphoma
(DLBCL) for subsequent scheduled CAR-T cell therapy (Kymriah®). e
median age was 56 (30-71) and 3 patients were female. In median the pa-
tients had received 4 prior treatments (3-6). Prior to apheresis the mean
white blood cell count (WBC) was 5500/µl (2000-14000) while absolute
lymphocyte count (ALC) was 640/µl (240-1390). All patients underwent a
large volume apheresis (4 x total blood volume) on a Spectra Optia device.
In 14/15 patients the target numbers of CD3+ cells were collected. e to-
tal count of collected CD3 cells was mean 6,8x109 (2,2-16,2), the yield was
mean 0,8x108/kg body weight (0,06-1,91). In 1 patient the collection was
performed in severe lymphopenia (240/µl) thus not reaching the minimal
yield of CD3+ cells. A consecutive collection aer one month was success-
ful. Vitality aer thawing reached >50% in all collections, median 82,1%
(68,8-94,2). Nevertheless, proliferation of lymphocytes aer transduction
in 3 collections (2 patients) was insucient thus terminating the produc-
tion of CAR T product.
Conclusions: In most patients intended to undergo real-life CAR T-cell
therapy adequate numbers of CD3 cells can be collected.
Reference:
1. Allen ES, Stroncek DF, Ren J, Eder AF, West KA, Fry TJ, Lee DW, Mackall CL,
Conry-Cantilena C. Autologous lymphapheresis for the production of chimeric
antigen receptor Tcells. Transfusion. 2017 May;57(5):1133-1141. doi: 10.1111/
trf.14003. Epub 2017 Feb 24.
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2018
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2018
Poster
255
Modulation of Antibody-Dependent Phagocytosis by
Macrophages under Metabolic Regulation in the Tumor
Microenvironment
Anna Beielstein 1, 2; Nadine Nickel 2; Elena Izquiero Alvalrez 2;
Daniela Vorholt 2; Samruddhi Schawan 2; Indra Möllenkötte 2;
Michael Hallek 1, 2; Christian P. Pallasch 1, 2
1Department I for Internal Medicine, University Hospital of Cologne, Cologne,
Deutschland
2CECAD Center of Excellence, CECAD Research Center, Cologne, Deutschland
Purpose: erapy response in B-cell lymphoma by chemoimmunother-
apy largely depends on the tumor microenvironment and the functional
status of macrophages as important eector cells. Within the tumor mi-
croenvironment a limited supply of nutrients leads to metabolic alter-
ations in malignant cells as well as an altered immune system.
Methods: As macrophage function is sensitive to metabolic alterations,
we addressed macrophage lymphoma cell co-cultures to assess the im-
pact of metabolic pathway inhibition (using several pathway inhibitors)
on antibody-dependent cellular phagocytosis (ADCP). We particularly
aim to improve macrophage eector cell function in the context of im-
munotherapy.
Results: Inhibition of AMP kinase, glycolysis or the ATP-production
had no positive eect on the phagocytosis rate. However, inhibiting the
pentose phosphate pathway (PPP) by Oxythiamine, p-Hydroxyphenylpy-
ruvate, Physcion and 6-Aminonicotinamide leads to an increased target
cell phagocytosis and Fc-receptor expression in independent eector cell
types (J774A1 and THP1). In this line metabolites of the PPP could be
shown to similarly aect ADCP by adding educts and products of the
PPP signicantly altering the macrophage-mediated target cell depletion.
ese changes could also be seen in PPP-enzyme knockdown (transketo-
lase and 6-PGD) in macrophages and by inhibiting the PPP in primary
murine and human macrophages.
We subsequently performed a proteomic analysis of PPP inhibition in
macrophages identifying metabolism and immune regulation related
eects. Specically under PPP-inhibition, Seahorse analysis showed in-
creased oxygen consumption and glycolysis of macrophages. Further-
more, the eector cells showed enlarged morphology and developed an
activated phenotype.
Conclusions: We hypothesize the PPP as a regulator of macrophage activ-
ity determining therapy outcome and aim to identify specic modulators
of macrophage polarization and function in tumor immunotherapy.
Disclosure Statement: No conict of Interest. A.B. was supported by Köln fortune
scholarship
482
A Phase 3 Randomized, Open-Label, Multicenter Study
Comparing Isatuximab, Pomalidomide, and Low-Dose
Dexamethasone Versus Pomalidomide and Low-Dose
Dexamethasone in Patients with Relapsed / Multiple Myeloma
Refractory (RRMM)
Dietger Niederwieser 1; Paul Richardson 2; Michel Attal 3; Vincent
Rajkumar 4; Jesus San-Miguel 5; Meral Beksac 6; Ivan Spicka 7; Xavier Leleu 8;
Fredrik Schjesvold 9, 10; Philippe Moreau 11; Meletios Dimopoulos 12;
Jerey Shang-Yi Huan 13; Jiri Minarik 14; Michele Cavo 15; Sandrine Macé 16;
H. Miles Prince 17; Kathryn P. Corzo 18; Frank Campana 18;
Solenn Le-Guennec 16; Franck Dubin 16; Kenneth C. Anderson on Behalf
of the Icaria-MM Study Group 2
1University of Leipzig, Leipzig, Deutschland
2Dana-Farber Cancer Institute, Harvard Medical School, Boston, United States
3Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, Frankreich
4Mayo Clinic, Rochester, United States
5Clínica Universidad de Navarra, Navarra, Spanien
6Ankara University, Ankara, Turkey
7Charles University in Prague, Prague, Tschechien
8Hopital Claude Huriez, CHRU Lille, Lille, Frankreich
9Oslo Myeloma Center, Oslo University Hospital, Oslo, Norwegen
10KG Jebsen Center for B cell malignancies, University of Oslo, Oslo, Norwegen
11CHU Nantes, Nantes, Frankreich
12National and Kapodistrian University of Athens, Athens, Griechenland
13National Taiwan University Hospital, Taiwan
14University Hospital Olomouc, Olomouc, Tschechien
15Univeristy of Bologna, Bologna, Italien
16Sano R & D, Vitry-Alfortville, Frankreich
17Epworth Healthcare and Peter MacCallum Cancer Centre, University of
Melbourne, Victoria, Australien
18Sano-Genzyme Oncology, Cambridge, United States
Purpose: To demonstrate the benet of isatuximab (Isa), a novel an-
ti-CD38 monoclonal antibody, combined with pomalidomide (P)/
dexamethasone (d) versus (vs) Pd, on progression free survival (PFS) in
RRMM patients (pts).
Methods: Pts who received ≥2 prior lines, including lenalidomide (len)
and a proteasome inhibitor (PI), refractory to last therapy were enrolled
in this phase 3 trial (NCT02990338). IsaPd arm received Isa 10 mg/kg IV
weekly for rst 4 weeks (wks), then every 2 wks. Both arms received ap-
proved schedules of P and d (4mg PO days 1-21; 40mg [20mg if >75 yrs]
PO or IV weekly) every 28 days until progression or unacceptable toxicity.
Results: 307 pts (154 IsaPd, 153 Pd) were randomized and analyzed (ITT).
Patient characteristics were well balanced across treatment arms. Medi-
an age: 67 (36-86) yrs; median prior lines of therapy: 3 (2-11); estimated
GFR: <60ml/min in 33.9% pts; 92.5% refractory to len, 75.9% to PI; and
19.5% pts had high-risk cytogenetics. At median follow-up (11.6 months
[mos]), median PFS was 11.5 mos IsaPd vs 6.5 mos Pd; HR 0.596 (95%
CI 0.44-0.81), P=0.001. PFS benet was consistent across all major sub-
groups. ORR (≥PR) was 60.4% IsaPd vs 35.3% Pd, P<0.0001. VGPR rate
or better was 31.8% IsaPd vs 8.5% Pd, and MRD negativity (NGS, 10-5)
was seen in 5.2% IsaPd pts vs 0% Pd. At analysis date, overall survival (OS)
was immature (99 events) but a trend to OS improvement in IsaPd vs Pd
was observed (HR 0.687; 95% CI 0.461-1.023). Median treatment dura-
tion was 41 wks IsaPd vs 24 wks Pd; median Isa infusion (inf.) duration
was 3.3h at 1st inf. and 2.8h at subsequent inf. Grade ≥3 AEs were observed
in 86.8% IsaPd vs 70.5% Pd; 7.2% IsaPd and 12.8% Pd pts discontinued
due to AEs; 7.9% IsaPd and 9.4% Pd pts died due to AEs. Inf. reactions
were reported in 38.2% (2.6% grade 3-4) IsaPd. Grade ≥3 infections were
seen in 42.8% IsaPd and 30.2% Pd, grade ≥3 neutropenia in 84.9% (febrile
11.8%) IsaPd and 70.1% (febrile 2.0%) Pd.
Conclusions: IsaPd signicantly improved PFS and ORR vs Pd, with a
manageable safety prole. IsaPd is an important new treatment option for
the management of RRMM.
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is abstract was previously presented atAmerican Society of Clinical
Oncology (ASCO)2019Annual Meeting, May 31–June 4, Chicago IL,
and encored at the European Hematology Association (EHA) June 13–16,
2019, Amsterdam, Netherlands
Disclosure Statement
DIETGER W. NIEDERWIESER: No conicts of interest.
PAUL G. RICHARDSON: Consulting or Advisory Role – Karyopharm; Onco-
peptides; Celgene; Janssen; Takeda; Sano; Research Funding - Oncopeptides,
Celgene; Takeda, BMS.
MICHEL ATTAL: Research Funding – Sano.
S. VINCENT RAJKUMAR: No conicts of interest.
JESUS SAN-MIGUEL: Consulting or Advisory Role - Amgen; Bristol-Myers
Squibb; Celgene; Janssen; MSD; Novartis; Roche; Sano; Takeda.
MERAL BEKSAC: Consulting or Advisory Role - Amgen (Inst); Celgene (Inst);
Janssen-Cilag (Inst); Takeda (Inst); Speakers’ Bureau - Amgen; Bristol-Myers
Squibb; Celgene; Janssen-Cilag.
IVAN SPICKA: Consulting or Advisory Role - Amgen; Bristol-Myers-Squibb;
Celgene; Janssen-Cilag; Novartis; Takeda; Speakers’ Bureau - Amgen; Bristol-
Myers-Squibb; Celgene; Janssen-Cilag; Novartis; Takeda.
XAVIER LELEU: Honoraria - Abbvie; Amgen; Bristol-Myers Squibb; Carsgen
erapeutics Ltd; Celgene; Janssen-Cilag; Karyopharm erapeutics; Merck;
Mundipharma; Novartis; Oncopeptides; Pierre Fabre; Roche; Sano; Takeda;
Consulting or Advisory Role - Abbvie; Amgen; Bristol-Myers Squibb; Carsgen
erapeutics Ltd; Celgene; Gilead Sciences; Janssen-Cilag; Karyopharm era-
peutics; Merck; Mundipharma; Novartis; Oncopeptides; Roche; Takeda; Travel,
Accommodations, Expenses – Takeda.
FREDRIK SCHJESVOLD: Honoraria - Abbvie; Amgen; Celgene; Janssen China
R&D; Novartis; Takeda; Consulting or Advisory Role - Adaptive Biotechnologies;
Amgen; Bayer; Bristol-Myers-Squibb; Celgene; Janssen China R&D; Oncopeptides;
Takeda; Research Funding - Amgen; Janssen China R&D.
PHILIPPE MOREAU: Honoraria - Amgen; Celgene; Janssen-Cilag; Novartis;
Takeda; Consulting or Advisory Role - Amgen; Celgene; Janssen; Novartis; Takeda.
MELETIOS A DIMOPOULOS: Honoraria -Celgene, Takeda, BMS, Janssen and
Amgen; Consulting or Advisory Role - Amgen; Bristol-Myers Squibb; Celgene;
Janssen-Cilag; Takeda.
JEFFREY SHANG-YI HUANG: Research Funding – Sano.
JIRI MINARIK: Consultancy and Honoraria - Amgen, BMS, Celgene, Janssen,
Takeda Clinical trials investigator - Amgen, Janssen, Karyopharm, Oncopeptides,
Sano.
MICHELE CAVO: Honoraria - Abbvie; Adaptive Biotechnologies; Amgen; Bristol-
Myers-Squibb; Celgene; GlaxoSmithKline; Janssen China R&D; Takeda; Consult-
ing or Advisory Role - Abbvie; Adaptive Biotechnologies; Amgen; Bristol-Myers-
Squibb; Celgene; GlaxoSmithKline; Janssen China R&D; Takeda; Speakers’
Bureau - Celgene; Janssen China R&D.
H. MILES PRINCE: Honoraria - Amgen; Celgene; Janssen China R&D; Novartis;
Takeda; Consulting or Advisory Role – Amgen; Celgene; Janssen China R&D;
Novartis; Takeda; Research Funding – Sano; Takeda.
KENNETH C. ANDERSON: Stock and Other Ownership Interests - C4 era-
peutics; OncoPep; Consulting or Advisory Role – Bristol-Myers Squibb; Celgene;
Gilead Sciences; Janssen Oncology; Millennium; Sano; Patents, Royalties, Other
Intellectual
Property - C4 erapeutics; Oncopep.
SANDRINE MACÉ, KATHRYN P. CORZO, FRANK CAMPANA, SOLENN
LEGUENNEC, FRANCK DUBIN are employees of Sano.
776
CAR T-Cell Therapy in the Real World Setting: Predictive
Factors for Successful Bridging between Apheresis and Car
T-Cell Infusion
Georg-Nikolaus Franke; Eberhard Schleyer; Konstantin Weibl;
Hansjakob Fries; Sophia Michel; Rosmarie Pointner; Dominic Brauer;
Andrea Hille; Sandra Otto; Uwe Platzbecker; Vladan Vucinic
Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I, Leipzig,
Deutschland
Purpose: CAR T-cells directed against CD19 are a newly approved cel-
lular therapy for treating patients (pts) with relapsed or refractory (r/r)
pediatric and adolescent acute lymphoblastic leukemia or diuse large
B-cell lymphomas (DLBCL). Bridging pts from lymphapheresis (LA) to
infusion of CAR T-cells remains challenging given the aggressive nature
of the disease. Little is known on predictive factors aecting this period of
manufacturing in the real-world population.
Methods: We evaluated the potential of clinical variables aecting success
of CAR-T reinfusion in pts receiving CD19 CAR tisagenlecleucel at our
CAR T-cell center.
Results: Nine pts were allocated to receive CARs and underwent apheresis
between May to August 2019 for r/r DLBCL. 3 pts died prior to infusion. 6
pts received CARs aer a median time of 49 days aer LA. Pts not receiv-
ing the CAR infusion presented with higher lactate dehydrogenase (LDH)
and C-reactive protein (CrP), worse ECOG performance status (PS) at the
time of LA, had obtained more lines of therapy and were more likely treat-
ed in an external hospital than patients receiving the CARs. We developed
a scoring system in order to predict outcome based on these factors. CrP
and LDH above the median were assigned 2 points (p.) each, the ECOG
PS at the time of LA were added, and each line of therapy aer 1st salvage
was assigned 1 p. and referral from an external hospital therapy 1 p. Pts
achieving a score of 5 or higher were at high risk to die prior to infusion:
3 out of 4 patients did not undergo CAR T-cell infusion. In contrast, pts
receiving the CARs had a median score of 2.5 (range 1-6).
Conclusions: Bridging eligible patients to from LA to CD19 CARs infu-
sion remains a challenge. e proposed score may help to identify pts at
high risk for complications rendering the CAR T-cell infusion impossible.
We aim to evaluate the score in a larger group of pts.
Disclosure: the authors have nothing to disclose
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Developmental Therapeutics: Molecular Therapeutics
Best-of-Abstracts-Vorträge
188
Identication of Novel Notch1-Regulated Therapeutic Targets
in Multiple Myeloma through Functional shRNA-Based
Screening
Daniela Simone Maichl 1; Fani Ziouti 1; Julius Arthur Kirner 1;
Stefanie Schmidt 1, 2; Carsten Patrick Ade 2; Sascha Dietrich 3;
Tobias Heckel 3; Franziska Jundt 1
1Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg,
Deutschland
2Universität Würzburg, Lehrstuhl für Biochemie und Molekularbiologie,
Würzburg, Deutschland
3Universität Würzburg, Core Unit Systemmedizin, Würzburg, Deutschland
Purpose: Aberrantly activated Notch signaling promotes multiple myelo-
ma (MM) onset, progression and drug resistance. As inhibition of Notch
activation using γ-secretase inhibitors is impeded by serious side eects,
there is still the need for the development of novel specic therapeutic
strategies. e present study aims to address this challenge and identify
novel druggable downstream eectors of the Notch1 pathway by employ-
ing shRNA-based functional high throughput (HT) screening.
Methods: First, we performed transcriptome proling in MM.1S cells to
identify Notch1-regulated genes. Of 842 genes dierentially expressed
aer Notch1 inhibition, we selected 40 consistently and strongly down-
regulated genes for a tailored shRNA library. Negative selection screens
employing the library were carried out in U266 cells modied to ex-
clusively express the Notch1 intracellular domain (NIC) or the Notch1
variant N∆E. Aer cultivation for 12 days under the selective pressure of
melphalan, bortezomib or lenalidomide, treated cells and controls were
harvested. Subsequently, shRNA sequences were recovered from genomic
DNA using PCR and changes in their representation were analyzed bioin-
formatically aer HT sequencing.
Results: Analysis of dierential shRNA representation of the rst screen
with lenalidomide was recently completed. Based on standard deviation
scores (z-scores; cut-o>-2), we ranked the shRNAs and further evaluat-
ed the druggability of the corresponding target gene/protein. Finally, we
chose 4 candidate genes - 3 transcription factors and one enzyme - drug-
gable with already available small molecule inhibitors. In vitro validation
of candidate genes will comprise treatment of MM cell lines with a chem-
ical inhibitor or specic shRNAs in combination with lenalidomide. Re-
sults of the bioinformatic analysis of the screens and in vitro validation of
screen hits will be presented in detail at the DKK 2020.
Conclusions: Study results hold the potential for the development of nov-
el MM treatment strategies.
Disclosure Statement: No conicts of interest.
Poster
563
NTRK Fusion-Tumors in Adult Cancer Patients – Single Center
Report on Screening and Treatment
Florian Länger 1; Hendrik Eggers 2; Ralf Gutzmer 3; Imke Satzger 3;
Christian von Falck 4; Arnold Ganser 2; Hans H. Kreipe 1; Viktor Grünwald 5;
Philipp Ivanyi 2
1Medizinische Hochschule Hannover, Institut für Pathologie, MHH, Hannover
2Medizinische Hochschule Hannover (MHH) Klinik für Hämatologie,
Hämostaseologie, Onkologie und Stammzelltransplantation, Hannover,
Deutschland
3Klinik für Dermatologie, Allergologie und Venerologie der Medizinischen
Hochschule Hannover, Hannover, Deutschland
4Medizinische Hochschule Hannover (MHH) Institut für Diagnostische
Radiologie, Hannover, Deutschland
5Westdeutsches Tumorzentrum Essen, Essen, Deutschland
Purpose: Neurotropic tropomyosin-related kinases (NTRK) are involved
in neuronal processes. Oncogenic NTRK gene-fusions are rare but prom-
ising targets for tyrosine kinase inhibitors (TKI). We report on feasibility
of screening and treatment of NTRK-fusions during oncology routine.
Methods: Patients (pts) with malignant diseases of mainly Head and
Neck (HNSCC), salivary glands (SGT), thyroid (TC), so tissue (STS),
bone (BS), kidney (RCC), melanocytes (MM) were screened. Primarily,
NTRK-immunhistochemistry (IHC) (EPR17341, Abcam) and FISH anal-
yses were done for ETV6 (Abbott Vysis). Once screening was positive,
RNA based NGS analyses was performed (RNA-Oncomine-Focus-Assay,
ermo Fisher). NTRK positive pts were treated with TKI larotrectnib, if
applicable.
Results: From 12/18-8/19 108 pts were screened. Pts were at median 53.7
(range (r), 15.8 - 89.9) years old and received 1.5 lines (r, 0 – 8) of che-
motherapy at time of screening. 3 (2.7 %) pts were NTRK-IHC positive,
and NGS conrmed NTRK-fusion in 2 pts (1.85 %) (TPM3-NTRK1 and
ETV6(5)-NTRK3(15)). One NTRK positive TC-pts received larotrectinib,
resulting in an ongoing good response.
Conclusions: NTRK testing is feasible during oncological routine upon
interdisciplinary established screening strategy. In 1.85 % of screened pts
NTRK-fusion-tumour was proven. is incidence is higher than expect-
ed, which might result from our selected screening cohort. However, in
one pts without therapeutic options NTRK screening enabled TKI admin-
istration resulting in highly eective treatment. Testing algorithm needs
to be discussed interdisciplinarily in particular when several NTRK inhib-
itors will be available, to ensure NTRK-inhibition as a therapeutic option
for patients with NTRK-fusion-tumours.
Dislosure Statement: FL, VG, PI received lecture honoraria and advisory fees
from Bayer and Roche.
723
Tumor-Biological Eects of Acetylsalicylic Acid and Ascorbic
Acid Regarding the HIF1 Level
Matthias Kappler 1; Ulrike Pabst 1; Dirk Vordermark 2; Alexander W. Eckert 1
1Department of Oral and Maxillofacial Plastic Surgery , Martin Luther University
Halle-Wittenberg, Halle (Saale), Deutschland
2Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle
(Saale), Deutschland
Purpose: Treatment with acetylsalicylic acid (ASA) positively aects the
prognosis of various tumor entities (Rothwell et al., 2012). A similar benet
for tumor patients was found for a treatment with ascorbic acid (vit c)
(Kuiper et al., 2014). It appears that the activity of the transcription factor
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HIF1 could be reduced by these treatments. HIF1 is a regulator of genes
involved in hypoxic metabolism/glycolysis but also inuences normoxic
metabolism/glutaminolysis. In addition, HIF1-level is associated with a
poorer outcome of tumor patients and drives the process of metastasis
(Rankin et al., 2016).
Methods: We examined in tumor cell lines the eect of ASA and vit c on
the expression of HIF1 and/or its tumor biological/metabolic inuence.
Results: We found that ASA and vit c reduced the expression level of nor-
moxic HIF1 and ASA even reduced the hypoxic HIF1 level. is is caused
by the ability of ASA to alter the acetylation status and thus the stability
of proteins (Tatham et al., 2017) like HIF1. Vit c appears to impair the
functionality of mitochondria and aected the normoxic HIF1 stability
and the amino acid metabolism, also independently of HIF1.
Conclusions: Both substances are able to inhibit the activity of HIF1. is
inhibition could partly explain the tumor-therapeutic eect of ASA and
vit c. A possible support of tumor therapies with ASA & vit c appears to
be a useful adjunction for the treatment of both normoxic and hypoxic
tumors.
References:
1. Tatham et al., MCP 2017, 16, 310–326.
2. Rothwell et al., e Lancet 2012, 379, 1602–1612.
3. Kuiper et al., Frontiers in oncology 2014, 4, 10.
4. Rankin et al., Science 2016, 352, 175–180.
Endocrine Tumor (e. g. Thyroid Cancer, Adrenal Tumor, Neuroendocrine Tumor)
Poster
589
Characterization of Epigenetic Modulation in Pancreatic
Neuroendocrine Neoplasms
Rosa Lynn Schmitz; Julia Weißbach; Jan Kleilein; Patrick Michl;
Sebastian Krug
University Hospital Halle (Saale), Clinic for Internal Medicine I, Halle (Saale),
Deutschland
Purpose: Pancreatic neuroendocrine tumors (pNETs) represent a rare
and heterogeneous tumor entity. Despite surgery, several therapeutic ap-
proaches involving biotherapy, target therapy or chemotherapy are appli-
cable. However, cancer progression and resistance mechanisms are still
challenging. Recent genome wide sequencing analyses in pNETs identi-
ed a large number of mutated genes involved in epigenetic modulation.
Targeting epigenetic regulation in tumor cells in combination with specif-
ically triggered immune cells could be a new therapeutic avenue.
Methods: e human pNET cell lines BON-1 and QGP-1, the murine in-
sulinoma cell lines beta-TC-6 and RIN-T3 and the human monocyte-like
THP-1 cells were treated with Panobinostat (PB) and analyzed for func-
tional eects and aected signaling pathways performing Western blot,
FACS and qPCR analyses. Additionally, the impact of PB on microRNA
and lncRNA expression in BON-1 and QGP-1 cells was investigated by
RNA sequencing.
Results: Beside hyper-acetylation, PB clearly induces an apoptotic phe-
notype as well as cell cycle arrest in neuroendocrine cells from various
species. ereby, the eect of PB tends to be mediated by a cluster of dif-
ferentially regulated microRNA and lncRNA. In THP-1 monocytes PB
induces altered macrophage polarization into a more pronounced M1
phenotype, which additionally enhances its tumor-repressing impact in
co-cultivation studies.
Conclusions: Beside its cytotoxic eect on tumor cells, PB also showed
tumor cell-independent inuence due to alteration of the inammatory
stroma. ese results play an important role on tumor progression.
Disclosure Statement: No conict of interest
703
“Routine Usage of Molecular Targeted Therapies (Everolimus
and Sunitinib) and Temozolomide Based Chemotherapy in
Neuroendocrine Neoplasia and Its Outcome
Sebastian Maasberg 1; Maria Bacher 2; Anja Rinke 3; Harald Lahner 4;
Detlef Quietzsch 5; Bence Sipos 6; Christian Grohé 7; Patricia Grabowski 8;
Nehara Begum 9; Christian Fottner 10; Ulrich-Frank Pape 1
1Innere Medizin, Gastroenterologie und Diabetologie, Asklepios Klinik St. Georg,
Hamburg, Deutschland
2Innere Medizin - Kardiologie und konservative Intensivmedizin, Vivantes
Humboldt Klinikum , Berlin, Deutschland
3Gastroenterologie, Endokrinologie, Stowechsel und klinische Infektiologie,
Universitätsklinikum Gießen Marburg, Standort Marburg, Marburg,
Deutschland
4Klinik für Endokrinologie und Stowechselerkrankungen, Universitätsklinikum
Essen, Essen, Deutschland
5Fachpraxis für Innere Medizin, Oelsnitz, Deutschland
6Fachärztliche Berufsausübungsgemeinschaft für Pathologie und
Molekularpathologie, Stuttgart, Deutschland
7Klinik für Pneumologie, Evangelische Lungenklinik Berlin, Berlin, Deutschland
8Institut für Immunologie, Universitätsmedizin Charité, Berlin
9Allgemein- und Viszeralchirurgie, Agaplesion Ev. Klinikum Schaumburg,
Obernkirchen , Deutschland
10I. Medizinische Klinik und Poliklinik, Schwerpunkt Endokrinologie und
Stowechselerkrankungen, Universitätsmedizin Mainz, Mainz, Deutschland
Purpose: Orally applied targeted therapies everolimus (EV) and sunitinib
(SUN) as well as a temozolomide (TEM) mono- or combination chemo-
therapy (CTx) with capecitabine (CAP) are of increasing importance in
the treatment of neuroendocrine neoplasia (NEN).
Methods: In a multicentric cohort from the German NET-Registry rou-
tine data of NEN pts. with initial diagnosis since 1988 were analyzed with
regards to the usage and outcome of EV, SUN and TEM-based therapies.
Statistical analysis was performed using SPSS version 20.0.
Results: From a total of 3521 patients (pts.) registered within the
NET-Registry database 219 received EV, 61 received SUN and 94 a TEM-
based CTx during the course of the disease. Subgroup analyses due to suf-
cient follow-up information were possible for 81 pts on EV, 36 on SUN
and 66 on a TEM-based CTx. In pts with EV, SUN or a TEM-based CTx
median age was 54 years, 56 years and 54 years, respectively. Primary tu-
mor localization were pancreatic (66%), bronchopulmonal (10%), intes-
tinal (13%) and other localizations (n=4%) or unknown (n=7%). Initial
therapy consisted of EV, SUN or TEM-based CTx in 9%, 6% or 10%, while
31%, 14% and 26% received them as second line treatment. In later ther-
apeutic lines EV was used in 60%, SUN in 77% and a TEM-based CTx in
64% of pts.. Partial remission (PR) as best radiologic response was seen
in 7% of pts. on EV, 23% of pts. on SUN and 24% of pts on a TEM-based
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CTx. Stable disease (SD) was achieved in 64%, 60% and 46% treated with
EV, SUN or a TEM-based CTx. Disease progression was documented in
29%, 17% and 30%, respectively. Median overall survival was 43 months
(m) in the EV group, while 44 m and 43m in the SUN or TEM-based CTx
group. Median time to documented progression (mTTP) was 8, 10 and
8 months in pts. with EV, SUN or a TEM-based CTx and 9 months in a
subgroup of pts. with NET-G2.
Conclusions: Routine treatment of EV; SUN and TEM-based CTx
showed a reasonable response and sucient disease control in advanced
and in part heavily pretreated pts. with neuroendocrine Neoplasia G1/G2
as well as G3.
827
Peritoneal Carcinomatosis Manifestation within the Hernia
Sack of an Inguinal Hernia (Representative Case)
Manuel Bachmann 1; Ste Peglow 1; Manuela Petersen 1; Victor Schoeder 2;
Dörthe Jechorek 2; Frank Meyer 1
1Dept. of General, Abdominal, Vascular and Transplant Surgery, University
Hospital at Magdeburg, Magdeburg, Deutschland
2Institute of Pathology, University Hospital at Magdeburg , Magdeburg,
Deutschland
Purpose: Periop. management & surgical treatment of inguinal hernia are
routinely provided.
Method: Scientic case report
Results (case presentation): A 65-years old patient w/ a med. history
signicant for a pararenal gland carcinoma (PRG-Ca) (treated w/ radia-
tion) w/ hepatic metastases & multiple ulcerations of the posterior gastric
wall showed reduced clinical (palpable & painful tumor resistance at the
right lower abdomen) & nutritional status (cachexia). CT scan showed
advanced tumor growth of a PRG-Ca inltrating surrounding organs.
A multivisceral resection was performed comprising adrenalectomy/le
nephrectomy, resection of the pancreatic tail, splenectomy, partial gastric
resection, resection of the le renal vein w/ tumor thrombectomy with-
in the inferior V. cava & patch plasty (xenogra), omentectomy & local
excision of peritoneal tumor lesions. Postoperatively, patient underwent
re-laparotomy to suture a sudden intestinal lesion. During further course,
an irreducible inguinal hernia was diagnosed which was conrmed by ul-
trasound & subsequently repaired by Shouldices procedure. e intraop.
suspicion of a peritoneal tumor lesion of the PRG-Ca within the herni-
al sac was conrmed by histopathological investigation. Further postop.
course was uneventful.
Conclusions: An irreducible inguinal hernia w/ manifest nodes of a peri-
toneal carcinomatosis can be assessed a rare but instructive disease in the
broad spectrum of dierential diagnoses of inguinal hernia.
Epidemiology
Poster
122
Socioeconomic Dierences and Lung Cancer Survival in
Germany: Investigation based on Population-Based Clinical
Cancer Registration
Isabelle Finke 1, 2; Gundula Behrens 1; Lars Schwettmann 3; Michael Gerken 4;
Ron Pritzkuleit 5; Bernd Holleczek 6; Hermann Brenner 1, 7, 8; Lina Jansen 1
1Division of Clinical Epidemiology and Aging Research, German Cancer
Research Center (DKFZ), Heidelberg, Deutschland
2Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Deutschland
3Institute of Health Economics and Health Care Management, Helmholtz
Zentrum München - German Research Center for Environmental Health
(GmbH), Neuherberg, Deutschland
4Tumor Center - Institute for Quality Management and Health Services
Research, University of Regensburg, Regensburg, Deutschland
5Institute for Cancer Epidemiology at the University of Lübeck, Cancer Registry
Schleswig-Holstein, Lübeck, Deutschland
6Saarland Cancer Registry, Saarbrücken, Deutschland
7Division of Preventive Oncology, German Cancer Research Center (DKFZ) and
National Center for Tumor Diseases (NCT), Heidelberg, Deutschland
8German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
Purpose: Studies from several countries reported socioeconomic inequal-
ities in lung cancer survival. Hypothesized reasons are dierences in can-
cer care or tumor characteristics. We examined associations of small-area
deprivation and lung cancer survival in Germany and the possible impact
of dierences in patient, tumor or treatment factors.
Methods: Patients registered with a primary tumor of the lung (ICD-10
C34) between 2000-2015 in three German population-based clinical can-
cer registries were included. Area-based socioeconomic deprivation on
municipality level was measured with the categorized German Index of
Multiple Deprivation (GIMD). Our main outcome, survival aer cancer
diagnosis, was analyzed with Cox regression and we repeated the analysis
for subgroups receiving chemotherapy, radiotherapy or surgery. e main
models included age, sex, histologic subtype, grading and stage at diagno-
sis. All analyses were conducted in SAS 9.4.
Results: Overall, 22,905 patients were included of whom 72.9% were
male, 23.8% were over 75 years of age, 49.5% were diagnosed with stage
IV cancer and 82.7% with non-small-cell lung cancer. Kaplan-Meier ve
year overall survival estimates from the least to the most deprived quintile
were 17.2% [95%-Condence Interval (CI): 15.8-18.5], 15.9% [14.8-17.2],
16.7% [15.5-17.9], 15.7% [14.5-16.9], and 14.4% [13.3-15.5], respectively.
Our main Cox model showed lower survival in the most deprived group
compared to the most auent group (Hazard Ratio (HR) 1.06, 95% con-
dence interval (CI) 1.01-1.11). Subgroup analyses showed lower survival
in the most deprived compared to the least deprived quintile for stage I-III
patients [HR: 1.14, 95% CI: 1.06-1.22]. e association persisted when re-
stricting to patients receiving surgery but was attenuated for subgroups
receiving either chemotherapy or radiotherapy.
Conclusions: Our results indicate dierences in lung cancer survival ac-
cording to area-based socioeconomic deprivation on municipality level
in Germany.
Disclosure Statement: e authors declare no conict of interest.
176
Establishing a Valid Approach for Estimating Familial Risk
ofCancer Explained by Common Genetic Variants
Korbinian Weigl 1; Jenny Chang-Claude 2; LI Hsu 3; Michael Homeister 1;
Hermann Brenner 1
1Deutsches Krebsforschungszentrum, Abteilung für Klinische Epidemiologie
und Alternsforschung, Heidelberg, Deutschland
2Deutsches Krebsforschungszentrum, Abteilung für Genetische Epidemiologie,
Heidelberg, Deutschland
3Fred Hutchinson Cancer Research Center, Public Health Science Division,
Seattle, United States
Purpose: To critically examine existing approaches for the estimation
of the excess familial risk of cancer which can be attributed to identi-
ed common genetic risk variants and to propose an alternative, more
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straightforward approach for calculating this proportion using well-estab-
lished epidemiological methodology.
Methods: e underlying equations of the traditional approaches and the
new epidemiological approach were applied for colorectal cancer (CRC)
in a large population-based case-control study in Germany with 4447 cas-
es and 3480 controls, who were recruited from 2003-2016 and for whom
interview, medical and genomic data were available.
Results: Having a family history of CRC (FH) was associated with a 1.77-
fold risk increase in our study population (95% CI 1.52-2.07). Traditional
approaches yielded estimates of the FH-associated risk explained by 97
common genetics variants from 9.6% to 23.1%, depending on various as-
sumptions. Our alternative approach resulted in smaller and more consis-
tent estimates of this proportion, ranging from 5.4% to 14.3%.
Conclusions: Commonly employed methods may lead to strongly diver-
gent and possibly exaggerated estimates of excess familial risk of cancer
explained by associated known common genetic variants. Our results
suggest that familial risk and risk associated with known common genetic
variants might reect two complementary major sources of risk.
Disclosure Statement: e authors have nothing to disclose.
398
Manifestation of Secondary Malignancies of the
Hematopoietic (HP) System in Patients with Tumors
of the Genitourinary (GU) Tract
Bernhard Koch 1; Lutz Uacker 1; Ayoub Abdu 1; Guntram Büsche 2;
Dirk Heimbach 3
1Datteln, St. Vincenz-Krankenhaus, Med. Klinik, Datteln, Deutschland
2Hannover, MHH, Institut für Pathologie, Hannover, Deutschland
3Datteln, St. Vincenz-Krankenhaus, Urologische Klinik, Datteln, Deutschland
Purpose: ere are reports on the increased risk of double malignancies
in patients with GU cancer and lymphomas (1,2). Since immunological
reactions play an important role in the control of tumor growth and since
the immune system is part of the HP system it seems of interest to look
more intensively on double malignancies arising in both systems to even-
tually detect common disturbances behind.
Methods: We searched the data base of our hospital over a period of 15
years for the documentation of double malignancies within the HP sys-
tem and the GU tract. e HP system was represented by acute leukemias
/ myelodysplasias (n=12), lymphomas / CLL (n=33), paraproteinemias /
multiple myelomas (n=12), and myeloproliferative diseases (n=2), and the
GU tract by cancer of the prostate (n=35), the bladder (n=19), and the
kidney (n=5).
Results: We identied 59 patients with double malignancies detected both
in the GU tract and in the HP system either synchronously or metachro-
nously (interval of diagnosis <3 or > 3 months). 66% of patients started
with a primary neoplasm of the GU tract followed by a HP malignancy
metachronously with a median interval time of 6 years. In 19 % of patients
the diagnosis of the HP and GU neoplasm was made synchronously. A
primary malignancy of the HP system was found in 15 % of patients. Rare
patients developed a HP malignancy within the GU tract. A group of 8
patients exhibited 3 malignancies of dierent entities.
Conclusions: Considering the multifactorial background of tumor
growth the occurrence of double malignancies may be associated to cyto-
genetic aberrations, therapeutic interventions, and perhaps immunosup-
pressive conditions due to chronic infections residing outside the tumor
itself in the tumor adjacent microenvironment. e analysis of patients
with multiple malignancies deserves special interest due to an advanced
cancer prone status.
References:
1. van den Broek EC et al., Ann Hematol 2014, PMID 24381068
2. Landgren O et al., Int J Cancer 2006, PMID 17131330
Disclosure Statement: e authors declare no conict of interest.
451
Trends in Cancer Survival in Germany from 1991 to 2016
Stefan Dahm; Benjamin Barnes; Klaus Kraywinkel
Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland
Purpose: Survival rates estimated using data from epidemiological cancer
registries in Germany are dicult to interpret due to regional and tem-
poral variability. One source of uncertainty is the substantial proportion
of cases notied by death certicate only (DCO cases). DCO cases are
usually excluded from survival estimation, but this can lead to biased sur-
vival rates.
Methods: is study is based on data from 4.6 million cancer patients
from 13 federal states diagnosed between 1990 and 2016 and expands
upon previous work [1]. First, relative survival rates were estimated ex-
cluding DCO cases for each registry and year. en, a mixed linear model
controlling for DCO proportions was tted to those estimates. Finally,
based on this model, survival rates and time trends for Germany were
estimated at a DCO proportion of 0%.
Results: e age standardized 1-year relative survival rates for all cancers
combined increased from 47% in 1991 to 73% in 2016, 5-year survival
rates increased from 1995 to 2016 by 25 percentage points to 60%. For
lung cancer, 1-year survival increased by 19 percentage points to 46% and
5-year survival increased from 9% to 18%. For pancreas cancer, 1-year
survival increased from 15% in 1991 to 40% in 2016 and 5-year survival
increased from 2% (1991) to 11% (2016).
Conclusions: e method presented here allows long-term survival
rate estimation based on data from several registries with varying DCO
proportions. Furthermore, the modelling approach uses recent data from
a large number of registries to strengthen estimates could be extended to
the time periods during which only three small registries were in operation.
Reference:
1. DAHM S. BERTZ J. BARNES B. KRAYWINKEL K. (2018) A mixed linear
model controlling for case underascertainment across multiple cancer
registries estimated time trends in survival. Journal of Clinical Epidemiology,
97C, 2018, pp. 123-133
Disclosure Statement: is research did not receive any specic grant from fund-
ing agencies in the public; commercial; or not-for-prot sectors
568
Educational Inequalities and Regional Variation in Colorectal
Cancer Survival in Finland
Isabelle Finke 1, 2; Karri Seppä 3; Nea Malila 3; Lina Jansen 1;
Hermann Brenner 1, 4, 5; Janne Pitkäniemi 6, 7
1Division of Clinical Epidemiology and Aging Research, German Cancer
Research Center (DKFZ), Heidelberg, Deutschland
2Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Deutschland
3Finnish Cancer Registry, Helsinki, Finnland
4Division of Preventive Oncology, German Cancer Research Center (DKFZ) and
National Center for Tumor Diseases (NCT), Heidelberg, Deutschland
5German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
6Department of Public Health, University of Helsinki, Helsinki, Finnland
7Faculty of Social Sciences, University of Tampere, Tampere, Finnland
Purpose: Previous studies reported lower colorectal cancer (CRC) sur-
vival in patients with lower educational levels. We investigated the impact
of regional variation on educational inequalities in CRC survival by using
both individual and aggregated area-based information on education.
Methods: Patients diagnosed with colorectal cancer (ICD-10 C18-20) in Fin-
land in 2007-2016 were followed up for death until end of 2016. Age-stan-
dardized relative survival and relative excess risk of death (RER) were es-
timated by sex using the period approach (Ederer II). RERs were adjusted
for follow-up time, age, stage at diagnosis, cancer site, urbanity and region
by using piecewise constant Poisson excess hazard models. All analyses were
conducted separately including individual (basic, secondary, high) and ag-
gregated area-based (quartiles Q1-Q4 based on the proportion of population
with basic education) information on education, respectively.
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2018
Index
2018
Results: Altogether 24,462 CRC patients diagnosed in 2007–2016 were
included in the analyses. ere was a clear gradient in 5-year relative sur-
vival across education groups (Men: Basic 61%, Secondary 64%, High
68%; Women: Basic 61%, Secondary 68%, High 71%). Compared to the
basic education group, RER in the high education group was 0.73 (95%
Condence Interval (CI) 0.65–0.82) in men and 0.67 (95% CI 0.59–0.76)
in women. Accounting for regional variation had no eect on the RERs,
but the eects were slightly attenuated when stage was adjusted for (RER
0.77 in men and 0.69 in women with high education). No association be-
tween area-based education and 5-year relative survival in men (Q1 63%,
Q2 64%, Q3 65%, Q4 63%) and women (Q1 61%, Q2 67%, Q3 69%, Q4
65%) was observed.
Conclusions: Educational inequalities in CRC survival are still present
in Finland and could not be explained by regional variations neither for
individual nor area-based education. Individual education information
should be preferred over area-based if interested in survival dierences
by education.
Disclosure Statement: e authors declare no conict of interest.
617
Record Linkage of 76,026 Cancer Cases Notied by Death
Certicate Only
Benjamin Barnes; Klaus Kraywinkel
Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland
Purpose: e federal cancer registry data act tasks the Robert Koch In-
stitute (RKI) with conducting an interstate data linkage to identify indi-
vidual cases reported by multiple epidemiological registries. e linkage
uses pseudonym control numbers based on patient names and dates of
birth. Because not all registries send control numbers to the RKI; a na-
tionwide linkage has not yet been possible. Methods: e current linkage
focused on matching cases notied by death certicate only (DCO cases)
in the years 2014 and 2015 with previously diagnosed cases. Data from 12
federal states covering 77% of the population were included. Due to the
limited identifying information available; a probabilistic approach was ap-
plied to identify likely matches. Results: A total of 76;026 DCO cases were
linked with approximately 8.5 million other cases. Of these DCO cases;
421 (0.6%) were identied as likely matches. Niedersachsen had the larg-
est proportion of likely matched DCO cases (1.4%). Analyses by county
(Landkreis) suggested particularly large numbers of likely matches in Ber-
lin and at the border between Lower Saxony and North Rhine-Westphalia.
Considering these cases as duplicates would reduce the estimated total
cancer incidence in Germany by far less than one percent. Conclusions:
Although the identication and elimination of duplicate records has only
a small impact on nationwide statistics; regional analyses – particularly at
state borders – may be aected to a greater extent. By focusing on DCO
cases; not only can duplicate records be identied; but vital status can be
updated for survival analyses.
620
Socioeconomic Deprivation and Burden of Cancer
in Baden-Württemberg
Volker Arndt 1, 2; Silke Hermann 1; Susanne Bergbold 1
1Deutsches Krebsforschungszentrum Heidelberg, Epidemiologisches
Krebsregister Baden-Württemberg, Heidelberg, Deutschland
2Deutsches Krebsforschungszentrum Heidelberg, Unit of Cancer Survivorship,
Heidelberg, Deutschland
Purpose: Socioeconomic disparity (SD) has been linked to dierences in
access to health care, cancer incidence, mortality, and prognosis but the
association between SD and stage at diagnosis is less well established [1-5].
Methods: Data from the Cancer Registry Baden-Württemberg on newly
diagnosed primary cancers between 2011 and 2017 were linked with com-
munity level SD from the German Index of Socioeconomic Deprivation
[6]. Dierences in cancer incidence were analyzed using multilevel Pois-
son regression models, in stage distribution (regional/distant vs. local/
in-situ) using chi²-test, and in age-adjusted survival using Cox propor-
tional hazards model with and without stage adjustment.
Results: Overall, there was a negative association between cancer inci-
dence and socioeconomic deprivation, i.e. lower rates were observed in
more deprived areas. is pattern was mostly pronounced for melanoma
and female breast cancer. Higher rates in more deprived areas were ob-
served for stomach cancer (males). e proportion of advanced tumors
was higher in socially more deprived areas for melanoma, colorectal
(males), breast and prostate cancer. Case fatality was higher in socially
more deprived areas for all cancers combined. Site and sex specic anal-
ysis revealed higher case fatality rates in more deprived areas for melano-
ma, stomach, prostate and thyroid cancer in males and for breast cancer
in females. Dierences in survival disappeared aer adjustment for dier-
ences in stage distribution.
Conclusions: Stage-adjusted prognosis does not vary according to so-
cioeconomic deprivation in Baden-Württemberg. e dierences in can-
cer incidence and stage distribution are most likely due to dierences in
screening behavior.
References:
1. Hoebel J et al. Front Oncol 2018; 8: 402
2. Hartung TJ, Johansen C. Forum 2017; 32: 318-23
3. Jansen L et al. Int J Cancer 2014; 134: 2951-60
4. Kuznetsov L et al. Int J Public Health 2012; 57: 827-35
5. Eberle A et al. J Public Health 2010; 18: 227-35
6. Kroll LE et al. J Health Monitoring 2017; 2: 103-20
Disclosure Statement: Nothing to disclose.
645
Human Papillomavirus Infections (HPV) in Young Women Ten
Years after the Introduction of HPV Vaccination in Germany:
The Nation-Wide HPV Prevalence Study
Viktoria Schönfeld 1; Adine Marquis 1; Sarah Thies 2; Amrei Krings 1;
Miriam Wiese-Posselt 1; Ole Wichmann 1; Andreas Kaufmann 2;
Thomas Harder 1
1Robert Koch-Institut, Infektionsepidemiologie, Berlin, Deutschland
2Charité Universitätsmedizin, Frauenklinik, Berlin
Purpose: Persisting infections with high-risk human papillomavirus
(HPV) can lead to cervical cancer. In 2007, routine HPV vaccination of
girls was introduced into the national vaccination schedule in Germany.
Vaccine coverage reached 44.6% in 2016. e two HPV vaccines on the
German market confer protection against two or seven high-risk HPV
types. Aim of our study was to investigate HPV prevalence in women aged
20-25 years and to estimate the eects of HPV vaccination ten years aer
the introduction of HPV vaccination.
Methods: We performed a nation-wide representative cross-sectional
study in 2017-18 using a two-step stratied sampling design to recruit
at least 1,173 women aged 20-25 years from population registries in
Germany. Participants used self-sampling kits (Evalyn brush; Rovers,
Oss, e Netherlands) to collect cervico-vaginal samples and completed
questionnaires. Samples were tested for 18 high-risk and eight low-risk
HPV types (genotyping HPV test; Optiplex; Diamex, Heidelberg).
Results: In 1,202 of 1,226 study participants HPV test results as well as
data on sociodemographic characteristics and HPV vaccination status
were available. Overall response rate was 15%, ranging from 10 to 18%
locally. Of 1,134 participants, 597 (53%) had received a full course of HPV
vaccine. Further analyses on HPV type prevalence and vaccine eective-
ness are in preparation and will be presented at the conference.
Conclusions: Our study will generate estimates of HPV type distribution
and assess the impact of HPV vaccination in Germany. ese data will
contribute to the evaluation of the national vaccination strategy and im-
prove prevention of HPV-associated carcinoma in Germany (supported
by BMG; grant no. 321-4471-02/158).
Disclosure Statement: All authors have nothing to disclose.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 47
Inhalt
2018
Index
2018
Gastrointestinal (Colorectal) Cancer
Best-of-Abstracts-Vorträge
533
High Microsatellite Instability (MSI-H) is Associated with
Distinct Clinical and Molecular Characteristics and an
Improved Survival in Early Colon Cancer (CC): Real Life Data
from the AIO Molecular Registry Colopredict Plus
Stefanie Nöpel-Dünnebacke 1; Hendrik Jütte 2; Celine Lugnier 1;
Dirk Arnold 3; Nadezhda Basara 4; T Dahm 1; Inke Feder 2; Wolfgang Hiller 5;
Torsten Herzog 6; Renate Klaassen-Mielke 7; Lothar Müller 8; Metin Senkal 9;
Gabriele Siegler 10; Christian Teschendorf 11; Guido Trenn 12;
Berlinda Verdoodt 2; Heiner Wolters 13; Waldemar Uhl 6;
Anke Reinacher-Schick 1; Andrea Tannapfel 2
1Abteilung für Hämatologie, Onkologie und Palliativmedizin, St. Josef Hospital
Bochum, Bochum, Deutschland
2Institut für Pathologie, Ruhr-Universität Bochum, Bochum
3Onkologie mit Sektion Hämatologie, Asklepios Klinikum Altona Hamburg,
Hamburg
4Medizinische Klinik 1, Malteser Krankenhaus St. Franziskus-Hospital, Flensburg
5Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Lippe GmbH,
Detmold
6Klinik für Allgemein- und Viszeralchirurgie, St. Josef Hospital Bochum, Bochum
7ABTEILUNG FÜR MEDIZINISCHE INFORMATIK, BIOMETRIE UND EPIDEMIOLOGIE,
Ruhr-Universität Bochum
8Onkologie UnterEms, Leer
9Klinik für Allgemein- und Viszeralchirurgie , Marien Hospital Witten , Witten
10Klinikum Nürnberg, Klinik für Innere Medizin 5, Nürnberg
11Klinik für Innere Medizin I, St. Josef Hospital Dortmund, Dortmund
12Klinik für Innere Medizin I, Knappschaftskrankenhaus Bottrop, Bottrop
13Klinik für Allgemein- und Viszeralchirurgie, St. Josef Hospital Dortmund,
Dortmund
Purpose: MSI-H is a known positive prognostic factor in early CC ob-
served retrospectively in numerous clinical trials. A prospective valida-
tion in real life cohorts, also compared to other molecular and clinical
factors, is still lacking.
Methods: From Sep 2013 to Jan 2019 patients (pts.) with UICC stage II/III
CC were registered in 70 German cancer centers. MS status was tested by
immunohistochemistry (IHC) of mismatch repair proteins. Loss of pro-
tein expression was conrmed by fragment length analysis (FLA) den-
ing MSI-H and MSS tumors. Mutational status in RAS, BRAF, PI3K was
determined by next generation sequencing (NGS). Disease free survival
(DFS) and overall survival (OS) were estimated using COX regression.
Relapse rates (RR) were calculated as a percentage of the subgroup.
Results: Tissue of 1787 pts. was analyzed by IHC and NGS. 423 pts. were
MSI-H upon FLA (23.7%). Association of MS status with clinical and mo-
lecular factors is shown in Table 1. Rate of MSI-H increased with age with
BRAF mutations (MT) more oen detectable in older MSI-H pts. (%BRAF
MT ≤70/70-75/>75y: 16.9/ 19.2/63.9%). DFS was signicantly longer in
MSI-H versus (vs.) MSS pts. (hazard ratio (HR) 0.702; condence interval
(CI) 0.547-0.900; p=0.005), while the HR for OS was not signicant due
to few events recorded (0.781; CI 0.595-1.0x26; p=0.076). DFS/OS in right
vs. le sided primary tumors were not dierent (HR 1.003 CI 0.844-1.192;
p=0.971/ HR 1.134; CI 0.930-1.383; p=0.213). In the BRAF MT subgroup,
RR was substantially lower in MSI-H vs. MSS pts. (5.2/19.7%) albeit RR in
MSI-H pts. did not dier between BRAF MT/WT (3.5/3.2%).
Conclusions: MSI-H tumors were more frequently detected in our cohort
compared to reported data, presumably related to the older age of our pts.
e high incidence of BRAF MT point to a sporadic etiology of most cas-
es. We could also conrm MSI-H as a strong prognostic marker in early
CC independent of BRAF MT.
Disclosure Statement: e authors state no disclosures.
Vorträge
678
Longitudinal Investigation of Circulating Tumour Cells
in Liquid Biopsies of Colorectal Cancer Patients - Analysis
of the Clinical Benet of a New Biomarker of Tumour Burden
and Relapse
Alexander Hendricks 1; Katharina Dall 2; Reinhild Geisen 3;
Christian Roeder 3; Susanne Sebens 3; Thomas Becker 2;
Clemens Schafmayer 1; Sebastian Hinz 1
1Universitätsmedizin Rostock, Klinik für Allgemeine-, Viszeral- und
Transplantationschirurgie, Rostock, Deutschland
2UKSH Campus Kiel, Klinik für Allgemeine- Viszeral- und Thoraxchirurgie, Kiel,
Deutschland
3Christian Albrechts Universität Kiel, Institut für Experimentelle
Tumorforschung, Kiel, Deutschland
Purpose: Previously, we established a semi-quantitative RT-PCR against
CK20 and were able to identify colorectal cancer (CRC) patients at risk.
Ongoing to this work, we now want to report on our recent longitudinal
data on serial CK20 mRNA analysis of CRC patients. For the rst time
this allows us to monitor the burden of the CTC over a course of time and
especially aer surgery and absence of the tumour.
Methods: In total 126 serial blood samples from 50 patients were anal-
ysed. Blood was drawn prior to surgery (t0), one month (t1), three (t2), six
(t3), nine (t4) and twelve months (t5) aer surgery. Blood samples were
analysed by CK20 RT-PCR. e PCR data was assessed regarding the pre-
viously published clinically relevant cut o value.
Results: At t0 17 (34.0%) patients were above the cut-o. At t1 a signif-
icant decrease of the CTC load was monitored (p<0.001). Also, at t2, t3
and t4 less CTC were measured (p=0.015, p<0.001, p=0.019, respectively).
ese results show, that the CTC load does correlate with the tumour bur-
den – aer macroscopically tumour free resection, the CTC load decreas-
es as no more tumorous tissue enables the release of CTC.
Analysing individual patients we exemplarily identied two patients. (A)
Stage II sigmoid carcinoma. Ongoing increase of mRNA expression over
the postoperative course of 12 months. At t6 the cut-o was passed. 14
months aer surgery a local relapse was diagnosed. (B) Stage III sigmoid
carcinoma. Adjuvant treatment was started. No elevated CTC in the rst
blood sample. T2: signicant increase of CTC passed the cut-o. Six
months postoperative, iliacal CRC metastasis.
Conclusions: We successfully implemented a protocol of obtaining and
analysing serial blood samples as liquid biopsies. By this, we might be able
to identify CRC patients who potentially benet of a more thorough aer-
care at an earlier stage of follow-up. e detection of CK20-positive CTC
may be a promising tool to detect a tumour recurrence prior to routine
radiological diagnostics.
Disclosure Statement: No conict of interest.
749
Laparoscopic and Open Resection of Rectal Cancer—is Age an
Eect Modier for Short- and Long-Term Survival?
Teresa Draeger 1, 2; Vinzenz Völkel 1, 2; Michael Gerken 1; Alois Fürst 1;
Monika Klinkhammer-Schalke 1
1Caritas Krankenhaus St. Josef, Regensburg, Deutschland
2Tumorzentrum Regensburg, Regensburg, Deutschland
Purpose: Various studies proofed the oncologic safety of laparoscopic
resection of rectal carcinoma. However, there does not exist a clear rec-
ommendation on whether age should inuence the choice of the surgical
approach.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts48
Inhalt
2018
Index
2018
Methods: is population-based retrospective cohort study compares
outcomes of laparoscopic and open surgery in rectal cancer patients.
Perioperative mortality, 5-year overall, relative, and recurrence-free sur-
vival rates were analyzed separately for three age groups (< 60 years, 60–69
years, 70–79 years). Data originate from 30 regional German cancer reg-
istries that cover approximately one quarter of the German population.
All primary nonmetastatic rectal adenocarcinoma cases with surgery
between 2005 and 2014 were eligible for inclusion. To compare survival
rates, Kaplan–Meier analysis, a relative survival model, and multivariable
Cox regression were used; a sensitivity analysis assessed bias by exclusion.
Results: 10,754 patients fullling all inclusion criteria without missing data in
important variables were included in the analysis. e mean laparoscopy rate
was 23.0% and increased over time. Uni- and multivariable regression anal-
ysis of 30-day postoperative mortality revealed advantages for laparoscopi-
cally treated patients, although the signicance level was not reached in any
age group (for age group 70–79, it was missed only slightly: odds ratio, OR
0.559; 95% condence interval, 95% CI 0.296–1.058). Regarding 5-year over-
all survival, laparoscopy generally seems to be the superior approach, whereas
for recurrence-free survival patients under 60 years beneted more from the
minimally invasive approach than older patients (< 60 years: hazard ratio, HR
0.703, 60–69 years: HR 0.787, 70–79 years: HR 0.923).
Conclusions: Laparoscopy shows similar results to the open approach in
terms of postoperative mortality in all age groups. Concerning long-term
outcomes, younger patients benetted most from the minimally invasive
approach. Increased use of laparoscopy for rectal cancer should be con-
sidered in this group.
756
Somatic Alterations and Tumor Mutational Burden (TMB) in
Patients with Metastatic Colorectal Cancer (mCRC) Treated
with FOLFiRI Plus Bevacizumab or Cetuximab (Fire-3 Trial)
Arndt Stahler 1; Sebastian Stintzing 2; Jobst C. von Einem 2;
C. Benedikt Westphalen 1; Nicole Krämer 3; Marlies Michl 1;
Dominik Paul Modest 2; Ludwig Fischer von Weikersthal 4; Thomas Decker 5;
Alexander Kiani 6; Tobias Heintges 7; Christoph Kahl 8; Frank Kullmann 9;
Werner Scheithauer 10; Markus Möhler 11; Ursula Vehling-Kaiser 12;
Thomas Kirchner 13; Andreas Jung 13; Volker Heinemann 1
1Klinikum der Universität München, Medizinische Klinik III, München,
Deutschland
2Charite - Campus Mitte, Medizinische Klinik mit Schwerpunkt Hämatologie
und Onkologie CCM, Berlin, Deutschland
3STABURO Statistical Consulting GmbH, München, Deutschland
4Klinikum St. Marien, Onkologie, Amberg, Deutschland
5Onkologische Praxis Prof. Dr. med. Thomas Decker, Ravensburg, Deutschland
6Klinikum Bayreuth GmbH, Medizinische Klinik IV, Bayreuth, Deutschland
7Rheinland Klinikum Neuss GmbH - Lukaskrankenhaus, Medizinische Klinik II,
Neuss, Deutschland
8Klinikum Magdeburg gemeinnützige GmbH, Abteilung für Hämatologie,
Onkologie und Palliativmedizin, Magdeburg, Deutschland
9Klinikum Weiden, Medizinische Klinik I, Weiden in der Oberpfalz, Deutschland
10Medizinische Universität Wien, Medizinische Klinik I & CCC, Wien, Österreich
11Universitätsmedizin Mainz, Medizinische Klinik I, Mainz, Deutschland
12Onkologische Praxis Dr. Ursula Vehling-Kaiser, Landshut, Deutschland
13Ludwig-Maximilian-Universität München, Pathologisches Institut, München,
Deutschland
Purpose: Molecular biomarkers and primary tumor sidedness guide
treatment decisions in mCRC. Precision oncology is a novel model to
identify targetable alterations and TMB.
Methods: FoundationOne® next generation sequencing (NGS) identied
single nucleotide variants (SNV), copy number alterations (CNA), TMB
and microsatellite instability (MSI-H) in patients treated in FIRE-3. Data
was correlated with overall response (OR), progression free survival (PFS)
and overall survival (OS). Multivariate regression analyses conrmed
prognostic and predictive biomarkers for OR.
Results: 373 of 754 patients (49.4 %) provided eligible material for this
analysis. Frequent known SNVs were found in TP53 (72.4 %), APC (66.0
%), KRAS (27.3 %), PIK3CA (16.1 %), BRAF (12.1 %), SMAD4 (8.0 %),
FBXW7 (7.0 %), frequent CNAs were found in FLT3 (5.6 %) and MYC
(6.7 %). RAS wildtype (WT) had signicantly longer OS (27.9 vs. 20.6
months, HR = 0.62 [95% CI 0.50 – 0.78], p = 0.0001) and PFS (10.4 vs
8.9 months, HR = 0.75 [95% CI 0.60 – 0.94], p = 0.01) compared to RAS
mutant (MUT) patients. OS (26.4 vs. 15.9 months, HR = 0.57 [95% CI
0.41 – 0.80], p = 0.001) and PFS (10.5 months vs 7.6 months, HR = 0.62
[95% CI 0.45 – 0.85], p = 0.003) were longer in BRAF WT vs. MUT pa-
tients. SMAD4 WT vs. MUT patients showed signicantly longer OS (HR
= 0.59 [95% CI 0.34 – 1.01], p = 0.05) and higher probability of response
[odds ratio SMAD4 SV vs. WT = 0.32 [95% CI 0.10 – 0.98], p = 0.05]
when treated with cetuximab. Multivariate regression conrmed BRAF,
KRAS and SMAD4 SNV as prognostic biomarkers and KRAS and SMAD4
MUT as predictive biomarkers for OR. High TMB (> 8 mutations / MB)
and MSI-H were detected in 56 and 10 patients, respectively, and showed
a trend towards better OR in patients receiving cetuximab.
Conclusions: RAS, BRAF and SMAD4 MUT were identied as poor prog-
nostic biomarkers in patients of FIRE-3. SMAD4 MUT might provide pre-
dictive relevance for cetuximab ecacy.
Poster
67
Dissemination of Intestinal Epithelial Cells in Inammation-
Associated-Colorectal- Carcinogenesis
Johanna Born 1; Alexander Hendricks 2; Alexander Bernsmeier 3;
Sascha Rahn 1; Christian Röder 1; Susanne Sebens 1
1Institut für experimentelle Tumorforschung, Christian-Albrechts-Universität zu
Kiel, Kiel, Deutschland
2Klinik für Allgemeine, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie,
UNIVERSITÄTSKLINIKUM Schleswig-Holstein, Kiel, Deutschland
3Sektion klinische Transplantation Klinik für Allgemeine, Viszeral-, Thorax-,
Transplantations- und Kinderchirurgie, UNIVERSITÄTSKLINIKUM Schleswig-
Holstein, Kiel, Deutschland
Purpose: Cellular markers for the detection of circulating tumor cells
(CTC) in patients with colorectal carcinoma (CRC) have been shown to
have a high predictive and prognostic relevance. Patients suering from
inammatory bowel diseases (IBD) have an increased risk to develop
colorectal cancer particularly aer long duration of disease. us, this
study investigated whether markers used for CTC detection in CRC
patients can be already determined in blood of IBD patients. Moreover,
detection levels were correlated with clinicopathological data such as
severity of inammation.
Methods: CK20, PLS3, LAD1, DEFA5 -mRNA expression was analyzed
by qRT-PCR in total RNA from peripheral blood mononuclear cell frac-
tion from patient blood samples provided by the biobank of Comprehen-
sive Cancer Center Kiel, Germany. In order to model the impact of an
inammatory microenvironment on malignancy-associated alterations
and expression of CTC markers, the intestinal epithelial cell line NCM-
460 was indirectly co-cultured with primary M1-like polarized human
macrophages in vitro.
Results: Markers used for CTC detection in CRC patients (n=100), par-
ticularly CK20 and PLS3, were also elevated in IBD patients (n=75) com-
pared to healthy donors (n=40). No dierence could be seen in the levels
of these markers in CRC or IBD patients. Current statistical analysis aims
at identifying a correlation between detection levels and clinical parame-
ters. Results from the in vitro co-culture system indicate that proinam-
matory macrophages inuence CTC marker expression as well as foster a
motile and mesenchymal phenotype in NCM-460 cells.
Conclusions: ese data suggest that dissemination of intestinal epithe-
lial cells into the blood is promoted by inammation and occurs already
in IBD patients. Further analyses are needed to understand the role and
evaluate the prognostic value of these CTC markers in IBD patients.
Disclosure Statement: e Authors declare no conict of interest.
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130
The Inuence of Postoperative Complications on Long-Term
Prognosis in Patients with Colorectal Carcinomas
Clemens Beck 1; Vera Schellerer 1; Klaus Weber 1; Maximilian Brunner 1;
Abbas Agaimy 2; Sabine Semrau 3; Robert Grützmann 1; Susanne Merkel 1
1Universitätsklinikum Erlangen, Chirurgie, Erlangen, Deutschland
2Pathologisches Institut, Universitätsklinikum Erlangen, Erlangen, Deutschland
3Universitätsklinikum Erlangen, Strahlenklinik, Erlangen, Deutschland
Purpose: e impact of postoperative complications (POCs) on long-
term prognosis in patients with colorectal carcinomas was analyzed with
respect to the severity of complications according to the Clavien-Dindo
classication (CDC).
Methods: e data of 2158 consecutive patients with curative elective
resection of a colorectal carcinoma (CME or TME/PME) without
distant metastases between 1995 and 2014 were analyzed. POCs were
documented in a standardized form and retrospectively assigned to
the CDC. Patients who died postoperatively (CDC grade V, 1.7%) were
excluded. e inuence of CDC on locoregional and distant recurrence,
disease-free and overall survival was examined.
Results: 990 patients with colon carcinoma and 1168 with rectal car-
cinoma were analyzed. 467 patients (21.6%) had POCs: CDC I 141
(6.5%), CDC II (pharmacological treatment) 162 (7.5%), CDC III
(surgical, endoscopical or radiological intervention) 112 (5.2%) and
CDC IV (intensive care) 52 (2.4%). A higher rate of POCs and a high-
er grade of CDC were found in men, ASA III-IV patients, rectal car-
cinomas, abdominoperineal excisions and multivisceral resections.
e 5-year rate of locoregional recurrences was 5.6% and was highest in
CDC grade III patients (12.9%). e 5-year rate of distant metastases was
16.7% and increased continuously to 23.7% in CDC grade IV patients. In
disease-free survival, the 5-year rate was 73.4% and decreased to 55.4%
in CDC IV patients. In overall survival, the 5-year rate was 81.3% and
decreased to 63.1% in CDC IV patients. is was conrmed in multi-
variate Cox regression analysis. We found a signicantly higher risk for
locoregional recurrences (HR 2.2; p=0.005) and distant metastases (1.7;
p=0.020) in CDC III patients, while patients with CDC grade IV were
associated with signicantly worse disease-free (HR 1.8; p=0.002) and
overall survival (HR 1.9; p=0.001).
Conclusions: Patients with POCs aer colorectal surgery have worse
long-term prognosis. With increasing CDC grade, survival deteriorates.
Disclosure Statement: e authors declare no conict of interest.
131
The Inuence of Body Mass Index on Long-Term Prognosis
in Patients with Colon Carcinomas
Susanne Merkel 1; Julian Fuchs 1; Vera Schellerer 1; Maximilian Brunner 1;
Carol Geppert 2; Robert Grützmann 1; Klaus Weber 1
1Universitätsklinikum Erlangen, Chirurgie, Erlangen, Deutschland
2Universitätsklinikum Erlangen, Pathologisches institut, Erlangen, Deutschland
Purpose: Obesity is an established risk factor for a number of chronic
diseases, including diabetes, cardiovascular diseases and cancer with an
unfavorable inuence on life expectancy. A crude measure of obesity is the
body mass index (BMI). Here, we analyze the impact of the preoperative
BMI on long-term prognosis in patients with colon carcinomas.
Methods: e data of 694 consecutive patients with curative resection of a
colon carcinoma (CME, complete mesocolic excision), no distant metas-
tases, between 2003 and 2014 were analyzed. BMI was categorized accord-
ing to the proposal of the WHO: <18.5 underweight, 18.5-24.9 normal
weight, 25.0-29.9 overweight, ≥30.0 obesity.
Results: 13 patients (1.9%) were underweight, 221 patients (31.8%) were
normal weight, 309 patients (44.5%) were overweight and 151 patients
(21.8%) were obese. Men were found to be signicantly more frequently
overweight or obese (p<0.001). e 5-year rate of locoregional recurrences
was 2.1%, no inuence of any risk factor including BMI was found. e 5-year
rate of distant metastases was 13.4%. It was signicantly higher in advanced
stage and emergency patients, but was not inuenced by the patients’ BMI.
e 5-year rate of disease-free survival was 72.4%, the 5-year rate of over-
all survival was 78.1%. Both were signicantly inuenced by age, ASA
classication, emergency presentation, tumor site, stage and preoperative
BMI. Obese patients had a signicantly better 5-year disease free surviv-
al than normal weight patients (78.5% vs 69.8%; p=0.045). is could be
conrmed in multivariate Cox regression analysis (HR 0.7; p=0.034). In
addition, obese patients had a signicantly better overall survival than
normal weight patients (82.4% vs 73.4%; p=0.027), which also could be
conrmed in multivariate Cox regression analysis (HR 0.6; p=0.019).
Conclusions: In a cohort of 694 colon carcinoma patients treated with
CME, obese patients at the time of surgery were not found to have worse
prognosis than normal weight patients.
Disclosure Statement: e authors declare no conict of interest.
223
Prognostic Value of BRAF, KRAS and MSI Status in Patients
with Advanced Left- and Right-Sided Colorectal Cancer: A
Retrospective Evaluation Based on Data from the Tumor
Documentation of the UCT Frankfurt
Maximilian Stohner 1; Corinna Bendfeldt 1; Gabriele Husmann 1;
Wolf O. Bechstein 2; Peter Wild 3; Stefan Zeuzem 4; Jörg Trojan 4;
Christine Koch 4; Ursula Pession 2; Christian Brandts 5
1Universitätsklinikum Frankfurt, Universitäres Centrum für Tumorerkrankungen:
Tumordokumentation, Frankfurt, Deutschland
2Universitätsklinikum Frankfurt, Zentrum der Chirurgie: Klinik für Allgemein-
und Viszeralchirurgie, Frankfurt, Deutschland
3Universitätsklinikum Frankfurt, Senckenberg Institut für Pathologie, Frankfurt,
Deutschland
4Universitätsklinikum Frankfurt, Zentrum der Inneren Medizin: Medizinische
Klinik I, Frankfurt, Deutschland
5Universitätsklinikum Frankfurt, Universitäres Centrum für Tumorerkrankungen,
Frankfurt, Deutschland
Purpose: In recent years, a large number of studies have dealt with the
prognostic dierence between advanced le- and right-sided colorectal
cancer (CRC). It became clear that patients with le-sided primarius have
a higher survival probability. Further studies linking certain molecular
markers such as KRAS, BRAF or MSI to the location showed an increase
in mutations on the right side. is issue will be further investigated using
data from the tumor documentation of the UCT Frankfurt.
Methods: For our study, we considered routine data from the UCT tu-
mor documentation on patients with advanced CRC (ICD-10 C18-20,
UICC III/IV) from 2008 until July 2019. We assigned exura linealis, co-
lon descendens, colon sigmoideum and rectum to the group of le-sided
carcinomas; caecum, appendix, colon ascendens, exura hepatica, colon
transversum were assigned to the right-sided tumors. Endpoint was the
overall survival aer 5 years (OS).
Results: 612 (78 %; total: 785) had a primary tumor on the le side. OS
was determined for patients with le-sided CRC at a rate of 47.2 % (95
% CI: 0.41 to 0.53), for patients with right-sided CRC at a rate of 37,2 %
(95 % CI: 0.28 to 0.46). In general, mutations could be detected more fre-
quently in the right-sided tumors. e survival could only be determined
in patients with mutated KRAS due to the small number of cases. ere
was no signicant dierence between le and right side.
Conclusions: As already proven in various other sources, the data of the
UCT tumor documentation also conrms the better prognosis for pa-
tients with le-sided CRC. As our results show, this could be associated
with a lower mutation rate compared to right-sided tumors. To conrm
this theory and for a more meaningful evaluation of the survival time of
the individual mutations, a further study with an increased number of
cases will be added.
References:
1. Petrelli, F. et al.: JAMA Oncol. 2017;3(2):211-219.
2. Sinicrope, F.A. et al.: JAMA Oncol. 2017;3(4):472-480
Disclosure Statement: All authors have declared no conicts of interest.
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264
Farkor: Evaluating a Screenig Program for Familial Colorectal
Cancer Risk
Sabine Homann 1; Alexander Crispin 1; Doris Lindörfer 1; Gaby
Sroczynski 2; Uwe Siebert 2; Ulrich Mansmann 1; Farkor Konsortium 3
1Institut für Medizinische Informationsverarbeitung, Biometrie und
Epidemiologie, Ludwig Maximilian‘s Universität, München, Deutschland
2Institut für Public Health, Medical Decision Making und HTA, Tiroler
Privatuniversität UMIT, Hall, Österreich
3Kassenärztliche Vereinigung Bayerns, München, Deutschland
Purpose: Colorectal cancer (CRC) screening in Germany starts at age 50.
As there is evidence that individuals with a family history of CRC have an
increased risk of developing CRC before age 50, screening for this group
should start earlier. is study evaluates the clinical and economic eects
of a risk-adapted screening program for CRC in individuals between 25
and 50 years of age.
Methods: An interim analysis assess the eects of the screening program
FARKOR (Family Related Colorectal cancer Risk) in a population-based
prospective cohort study. e program is open to members of the statu-
tory health insurance in Bavaria between October 2018 and March 2020.
Participants enter the study through their physicians or a public cam-
paign. Additionally, insurances contact patients recently diagnosed with
CRC to inform them that their relatives may have an increased risk of
developing CRC. Trained doctors classify participants as potential risk
carriers or as inconspicuous. Potential risk carriers are invited to a shared
decision making shared decision making on 1) immunological test for
fecal occult blood or 2) colonoscopy. Assessment of long-term benets,
harms and cost-eectiveness of FARKOR uses decision-analytic modeling
from the perspective of the German health care system.
Results: Aer 11 months, 4823 patients have joined the program. Among
the 1675 identied potential risk carriers, 1201 participated in a shared
decision making aer which 421 (635) decided to undergo an immuno-
logical test for fecal occult blood (colonoscopy). Adenoma were detected
in 17% of screening colonoscopies. No complication occurred.
Conclusions: e preliminary results of an interim analysis suggest good
adherence to the proposed screening measures. Further evaluations will
follow to assess its overall clinical and economic eects.
Disclosure Statement: e “German Innovation Fund” of the Federal Joint Com-
mittee (G-BA) supports this work: 01NVF17026. e author declare no conict of
interest.
341
IVOPAK II Study: Morbidity Following Secondary Resection
of Colorectal Liver Metastases
Vera Schellerer 1; Susanne Merkel 1; Robert Grützmann 1;
Stephan Kersting 1; Axel Wein 2
1Chirurgische Klinik des Universitätsklinikums Erlangen, Erlangen, Deutschland
2Medizinische Klinik 1- Gastroenterologie, Pneumologie und Endokrinologie
des Uni-Klinikums Erlangen, Erlangen, Deutschland
Purpose: In the IVOPAK II study, patients with unresectable metastatic
colorectal carcinoma (CRC) receiving palliative chemotherapy and bio-
logical agents aer expanded RAS-analysis are regularly re-staged by im-
aging with subsequent tumor board decision every 2 months to identify
patients becoming secondary resectable.
Methods: Between 7/2016 and 7/2019, 40 patients were included into the
study. 50% (n=20) had a RAS mutation, 50% (n=20) an All-RAS-wildtype.
To date, 14 patients received a secondary curative therapy, including 9 pa-
tients with liver metastases only (HEP), 1 patient with resection of HEP
and primary tumor (PT), 2 patients with resection of HEP and pulmonary
metastases (PUL) and PT, 1 patient with resection of PUL, 1 patient with
peritoneal metastases.
Results: Median age of the 12 patients with HEP was 65 years (range:
56-72), including 10 men and 2 women. RAS wildtype was diagnosed in
67% (n=8), RAS mutations in 33% (n=4). Patients underwent secondary
curative surgery in median 6 months aer starting palliative treatment
(range 3-18). e 12 patients with HEP (+/- PUL) were treated by surgical
resection (n=7), radiofrequency ablation (n=3), both (n=2). Liver resec-
tions included 2 atypical and 4 segmental resections, 2 right hemihepatec-
tomies and 1 extended right hemihepatectomy. Postoperatively, the fol-
lowing complications occurred in liver-resected patients (Clavien-Dindo
classication): Grade 0 (n=2), Grade I (n=1), Grade II (n=1), Grade III
(n=2), Grade III (n=3). Median follow-up of the 12 patients is currently
6 months (0-28). 11 of 12 patients are still alive. 4 patients (30%) remain
with no evidence of disease.
Conclusions: Even in patients with unresectable metastatic CRC receiv-
ing palliative therapy, regularly restaging for evaluation of secondary cu-
rative treatment options is meaningful. e high response rate of All-RAS
wildtype population is important for secondary resection.
Disclosure Statement: e authors declare no conict of interest.
348
Case of Two Patients with MSI-High Metastatic Colorectal
Cancer Treated with Pembrolizumab
Annika Kurreck 1; Sebastian Stintzing 2; Dominik Paul Modest 1; Ivan Jelas 3;
Jobst C. von Einem 2
1Charité University Medicine Berlin, Department of Hematology, Oncology, and
Tumorimmunology (CVK), Berlin, Deutschland
2Charité University Medicine Berlin, Department of Hematology and Oncology
(CCM), Berlin, Deutschland
3Charité University Medicine Berlin, Charité Comprehensive Cancer Center,
Berlin, Deutschland
Purpose: Immune checkpoint inhibitors (ICI) have become a standard
treatment in everyday oncological practice. In clinical trials, pembroli-
zumab and nivolumab as well as the combination of nivolumab and
ipilimumab have demonstrated ecacy in patients with microsatellite
instability-high (MSI-high) metastatic colorectal cancer (mCRC). e
underlying mismatch repair deciency seems to correlate with the lev-
el of neoantigen and consecutively with high immunogenicity- this may
explain the treatment eect derived from ICI in MSI-high mCRC. Unlike
the FDA, the EMA has not yet approved ICI for the treatment of MSI-
high mCRC.
Methods: We present a scientic report on the clinical courses of two
male patients with RAS-wildtype, MSI-high mCRC, who received o-la-
bel pembrolizumab (200 mg every 3 weeks) in our department aer fail-
ure to rst- and third-line treatment, respectively.
Results: A 42-year old patient with synchronous hepatic mCRC received
pembrolizumab aer tumor progress to rst-line treatment with FOLFI-
RI and Cetuximab. e patient developed signicant clinical symptoms
and corresponding radiological tumor progression aer four administra-
tions of ICI. We administered pembrolizumab as fourth-line treatment to
another 49-year old patient with mCRC, that metastasized per continui-
tatem to the right-sided thoracic wall. Aer three applications, a CT-scan
revealed signicant shrinkage of the bulky tumor mass. e radiological
re-assessment ve months aer initiation demonstrated further decreas-
ing tumor size. e clinical performance status improved signicantly and
therapy with pembrolizumab is still ongoing.
Conclusions: ICI are able to provide durable tumor response in pretreat-
ed MSI-high mCRC patients. erefore, we emphasize the importance
of testing for MSI. Further clinical studies are needed in order to verify
ecacy and safety of ICI in mCRC patients and to identify those patients
with MSI-high mCRC that do not benet from ICI therapy.
Disclosure Statement: No conict of interest.
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349
Age-Specic Sequence of Colorectal Cancer Screening oers
in Germany: Model-Based Critical Evaluation
Thomas Heisser 1, 2; Korbinian Weigl 1, 3; Michael Homeister 1;
Hermann Brenner 1, 3, 4
1Clinical Epidemiology and Aging Research, German Cancer Research Center
(DKFZ), Heidelberg, Deutschland
2Medical Faculty, University of Heidelberg, Heidelberg, Deutschland
3German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
4Division of Preventive Oncology, German Cancer Research Center (DKFZ) and
National Center for Tumor Diseases (NCT), Heidelberg, Deutschland
Purpose: e current oer of the organized screening program for col-
orectal cancer (CRC) in Germany implies that both sexes can have up to
ve annual fecal immunochemical tests (FITs) between ages 50-54, fol-
lowed by a rst screening colonoscopy at age 55 in case all of these FITs
were negative. We sought to assess the performance of this oer.
Methods: Using a multistate Markov model, we quantied the expected
prevalences of neoplasms in a population perfectly adhering to annual FIT
screening between ages 50-54 to assess the detection rates and numbers
needed to scope one case of (non-)advanced adenoma or cancer (NNS) of
colonoscopic screening at age 55. We additionally modelled the diagnostic
performance of such consecutive annual FIT testing.
Results: In subjects with ve consecutive negative FITs, expected colo-
noscopy detection rates (NNS) of any neoplasm, any advanced neoplasm
and cancer at age 55 are 10% (10), 1.9% (52) and 0.05% (2,089), respec-
tively, in women, and 17% (6), 3.5% (28) and 0.09% (1,058), respectively,
in men. Positive predictive values (PPVs) for advanced neoplasms drop
from 14.0% and 22.4% in year 1 to 8.4% and 13.9% in year 5, and PPVs
for cancers from 2.4% and 3.9% to 0.6% and 1.0%, for women and men,
respectively.
Conclusions: Our ndings suggest that the current screening oer in
Germany of ve consecutive FITs from ages 50-54, followed by screening
colonoscopy at age 55 aer ve negative FITs, may be highly inecient as
perfect adherence would go along with very low PPVs of repeat annual
FITs and very high NNS of screening colonoscopy at age 55. e design of
the FIT screening oer should be re-evaluated.
Disclosure Statement: e authors declare that they have no conict of interest.
352
Outcomes at Follow-Up of a Negative Colonoscopy
in the Average-Risk Population: a Systematic Review
and Meta-Analysis
Thomas Heisser 1, 2; Le Peng 1, 2; Korbinian Weigl 1, 3; Michael Homeister 1;
Hermann Brenner 1, 3, 4
1Clinical Epidemiology and Aging Research, German Cancer Research Center
(DKFZ), Heidelberg, Deutschland
2Medical Faculty, University of Heidelberg, Heidelberg, Deutschland
3German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
4Division of Preventive Oncology, German Cancer Research Center (DKFZ) and
National Center for Tumor Diseases (NCT), Heidelberg, Deutschland
Purpose: To review and summarize the evidence on the prevalence of col-
orectal adenomas and cancers at a follow-up screening colonoscopy aer
negative index colonoscopy, stratied by interval between examinations
and by sex.
Methods: We systematically searched the electronic databases of PubMed,
Web of Science and EMBASE and performed meta-analyses of all avail-
able studies. Published studies were eligible for inclusion if they assessed
the outcome of a follow-up colonoscopy in subjects at average risk for
CRC with a negative previous colonoscopy (no adenomas).
Results: 28 studies were identied, including 22 cohort studies, 5
cross-sectional studies and 1 case-control study. Findings for an interval
between colonoscopies of one to ve, ve to ten, and more than ten years
were reported by 17, 16 and 3 studies, respectively. Summary estimates
(95% condence intervals) of rates of any neoplasms were 20.7% (15.8%
to 25.5%), 23.0% (18.0% to 28.0%) and 21.9% (14.9% to 29.0%) for one to
ve, ve to ten, and more than ten years between colonoscopies. Corre-
sponding summary estimates of rates of advanced neoplasms were 2.8%
(2.0% to 3.7%), 3.2% (2.2% to 4.1%) and 7.0% (5.3% to 8.7%). Seven stud-
ies also reported ndings stratied by sex. Summary estimates stratied by
interval and sex were consistently higher for men as compared to women.
Conclusions: Although detection of any neoplasms was observed in >20%
of subjects within ve years of a negative screening colonoscopy, detection
of advanced neoplasms within ten years was rare. Our ndings suggest
that ten-year colonoscopy screening intervals aer negative colonoscopy
(as currently recommended) may be adequate, but more studies are need-
ed to strengthen the empirical basis for pertinent recommendations and
to investigate even longer intervals.
Disclosure Statement: e authors declare that they have no conict of interest.
377
Long Term Survival of Patients with Stage IV Rectal
Cancer - Due to Targeting the Tumor Associated
Inammatory Process?
Bernhard Koch 1; Lutz Uacker 1; Ayoub Abdu 1; Andrea Tannapfel 2
1Datteln, St. Vincenz-Krankenhaus, Datteln, Deutschland
2Bochum, Institut für Pathologie, Bochum, Deutschland
Purpose: e median overall survival time of patients with stage IV rectal
cancer is less than 3 years. We present cases of 2 patients with rectal cancer
who survived initial diagnosis of metastasis for 9 and more than 11 years,
respectively. We speculate on the possible reason for this favorable course.
Case reports: Patient 1 was a 66 year old lady who was operated because
of rectal cancer UICC stage I. 18 months later she developed skin and
hepatic metastasis, received resection and was treated with regimens
containing FOLFOX, bevacizumab, FOLFIRI, cetuximab, irinotecan,
CAPOX, panitumumab, mitomycin, and aibercept. She died 9 years aer
diagnosis of metastasis. Patient 2, aged 61 years, initially presented with
metastasis to the peritoneum and later on to abdominal wall and lung.
During the course she was treated with regimens containing bevacizum-
ab, FOLFIRI, capecitabine, FOLFOX, cetucimab, and ramucirumab. She
received several tumor resections and irradiation. Currently she is living
more than 11 years aer diagnosis of metastasis.
Discussion: A survival of more than 9 years in stage IV rectal cancer is re-
markable. Based upon animal studies a strategy combining antiangiogenic
therapy with long term applcation of capecitabine has been proposed (1).
In the human situation single cases of the benecial eects of long term
metronomic capecitabine have been reported. e patients described
here received a long term therapy with regimens containing anti-VEGF,
or VEGFR-2 directed modalities, and drugs targeting endothelium and
tumor supporting myeloid cells.
Conclusions: Besides targeting tumor cells itself the long lasting inhib-
tion of angiogenesis proves to be an important factor to achieve long term
disease stabilisation.
e spectrum of drugs targeting cells of the intra- and peritumoral in-
ammatory rection is wide and aggravates the interpretion of single fac-
tors responsible for a benecal course.
Report more of those cases with a noticeable survival time.
Reference:
1. Zhang Y et al, PNAS 2017, PMID: 28607065
Disclosure Statement: e authors declare no conict of interest.
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Real-World Testing Patterns for Braf-Mutations and Treatment
of Patients with Braf-Mutated Metastatic Colorectal Cancer:
Results from The German Tumor Registry Colorectal Cancer
(TKK Registry)
Mark-Oliver Zahn 1; Steen Dörfel 2; Holger Schulz 3; Thomas Wolf 4;
Ursula Vehling-Kaiser 5; Susanne Tech 6; Martina Jänicke 6; Natalie Wetzel 6;
Norbert Marschner 7
1Studienzentrum MVZ Onkologische Kooperation Harz, Goslar, Deutschland
2Onkozentrum Dresden/ Freiberg, Dresden, Deutschland
3Praxis Internistischer Onkologie und Hämatologie (PIOH), Frechen,
Deutschland
4BAG / Onkologische Gemeinschaftspraxis, Dresden, Deutschland
5Hämatologisch-onkologische Tagesklinik, Landshut, Deutschland
6iOMEDICO, Freiburg, Deutschland
7Praxis für Interdisziplinäre Onkologie & Hämatologie, Freiburg, Deutschland
Purpose: BRAF-mutations have been reported in approximately 8-12 %
of patients (pts) with metastatic colorectal cancer (mCRC), with V600E
being the most common mutation. Despite major improvements in sur-
vival for mCRC overall, BRAF-mutant mCRC typically appears refractory
to standard chemotherapy for mCRC and is associated with a poor prog-
nosis with a median overall survival of less than 12 months. Real-world
data on the identication and treatment of this high medical need popu-
lation are scarce.
Methods: Since 2006, the Tumor Registry Colorectal Cancer (TKK) pro-
spectively documents treatment of CRC pts in clinical routine in Germa-
ny. Pts are treated according to physicians choice. Data on pts and tumor
characteristics, all systemic treatments including rst-line and subsequent
line treatments, outcome and quality of life are collected. In addition,
since 2018 data on BRAF testing are documented. Here, we analyzed
BRAF-mutation testing patterns and treatment of pts with BRAF-mutant
mCRC. Analyses were ongoing at the time of submission.
Results: Until data base cut 31.03.2019, 4334 pts with mCRC had been
enrolled at initiation of palliative rst-line treatment, 474 pts from 91 sites
since data on BRAF testing is collected. Of those, 65% (310 pts) were test-
ed for BRAF mutation with positive results documented in 48 patients
(10% of all, 15% of tested pts). Results will be presented regarding charac-
teristics (age, gender, ECOG performance status, tumor localization, RAS
status, MSI status, time between primary diagnosis until start of rst-line
therapy) and treatment patterns (1st, 2nd, 3rd line) of pts with and without
BRAFmutation testing and with and without BRAF mutation.
Conclusions: is analysis of the TKK data provides important insights
into the testing and treatment patterns of patients with BRAF-mutant
mCRC treated in clinical routine in Germany.
Disclosure Statement: None of the authors has declared a conict of interest
regarding the subject of this work.
466
Perioperative Therapy of Locally Advanced Adenocarcinoma
in the Upper Third of The Rectum - Long-Term Results
of Dierent Therapeutic Approaches
Johannes Reber 1; Michael Gerken 1; Teresa Draeger 2; Sophia Scharl 3;
Vinzenz Völkel 4; Alois Fürst 4; Monika Klinkhammer-Schalke 1
1Tumor Center, Institute for Quality Management and Health Services Research,
University of Regensburg, Regensburg, Deutschland
2Caritas Krankenhaus St. Josef Regensburg, Klinik für Innere Medizin,
Regensburg, Deutschland
3Department of Radiation Oncology, Klinikum rechts der Isar, Technische
Universität München (TUM), München, Deutschland
4Caritas Krankenhaus St. Josef Regensburg, Klinik für Allgemein-, Viszeral-,
Thoraxchirurgie und Adipositasmedizin, Regensburg, Deutschland
Purpose: e German S3-guidelines recommendations for the perioper-
ative treatment of stage II and III rectal cancer in the upper third of the
rectum have recently changed. Between 2008 and 2017 it was up to the
treating physician whether to follow the guidelines recommendations on
rectum- or on colon carcinoma; nowadays, there is a clear statement in
favor of the colon line of treatment.
Methods: Based on a cohort of 5,312 patients diagnosed with stage II/
III upper third rectum cancer between 2000 and 2016, gathered by 30
clinical cancer registries in Germany, we performed a comparison of 462
cases of neoadjuvant radiochemotherapy and adjuvant chemotherapy
combined and 1,049 cases of adjuvant chemotherapy only, with regard to
the outcome quality of the dierent perioperative therapeutic approaches
for locally advanced upper third rectum cancer in clinical practice. Us-
ing Kaplan-Meier, uni- and multivariable Cox-regression analyses, over-
all survival, disease-free survival, local and distant recurrence rates were
calculated.
Results: Patients in UICC stage II/III who received neoadjuvant
radiochemotherapy and adjuvant chemotherapy combined had, according
to the multivariable analyses, no signicant dierences concerning
overall survival, disease-free survival or local and distant metastases
rates as compared to patients receiving adjuvant chemotherapy only.
e corresponding cumulative 5-year local recurrence rates were 4,1%
and 5,6% respectively. In contrast, patients with UICC stage III and an
elevated risk prole (subgroup analyses for: stage III T4 and stage III N2)
showed a signicantly worse disease free survival when they had obtained
adjuvant chemotherapy only (HR=3,225, 95%-CI=1,140-9,123, p=0,027 /
HR=2,352, 95%-KI=1,153-4,798, p=0,019).
Conclusions: e recommendations of the German S3-guideline of 2017
to refrain from neoadjuvant radiation therapy in low-risk patients with
a tumor in the upper third of the rectum are supported by the results of
this study.
Disclosure Statement: e authors declare no conict of interest.
512
The Inuence of Diabetes Mellitus (DM) on Morbidity and
Mortality as well as Oncological Outcome in Colon Cancer (CA)
Surgery – Interims Analysis
Romy Kreyer 1; Ronny Otto 2; Stefanie Wol 1; Ingo Gastinger 2;
Hans Lippert 2; Henry Ptok 1; Roland S. Croner 1; Frank Meyer 1
1Dept. of General, Abdominal, Vascular and Transplant Surgery, University
Hospital at Magdeburg, Magdeburg, Deutschland
2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg, Deutschland
Purpose: To investigate the inuence of DM as well as the factors associ-
ated with this metabolic disease, on early postop. & long-term oncological
outcomes following colon Ca surgery.
Methods: Patients with colon Ca -/+ DM were registered in this prospec-
tive multi-center observational study. Early postop. & long-term onco-
logical outcome was specically characterized by morbidity/in-hospital
mortality & 5-yr-overall survival (5-yr-OS), 5-yr-disease-free survival
(5-yr-DFS) & 5-yr-local recurrence rate (5-yr-LRR), resp.
Results: In total, 9167 patients were enrolled who were subdivided as fol-
lows: 20.5% w/ DM (insulin-dependent, 37.8%) & 79.5% w/o DM (age
range of +/- DM patients, 34-97 vs. 18-98 yr; sex ratio [m/f], 52.9/47.1%
vs. 56,2/43,8%). e initially higher progression rates of tumor (Tu) dis-
ease (P=0.018) as well as the more advanced Tu stages according to the
UICC classication was found in DM patients (P=0.293). Furthermore,
DM patients showed signicantly worse ASA scoring (P<0.001). With
a total morbidity of 35.8%, DM patients had signicantly more general
postop. complications (P<0.001). However, the slightly higher rate of spe-
cial postop. complications in DM patients was not signicant (P=0.224).
With a total in-hospital mortality of 4.2%, DM patients showed a signi-
cantly higher rate (P<0.005). DM patients had a signicantly lower 5-yr-
OS (DM, 49.8% vs. non-DM 59.7%; P<0.001). A clearly worse 5-yr-DFS
was also found in the DM category (DM, 57.7% vs. non-DM, 67.6%,
P<0.001). e surprisingly lower 5-yr-LRR of DM vs. non-DM patients
was not signicant (2.4% vs. 2.8%, P=0.664).
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2018
Index
2018
Conclusions: e highest postop. complication rates as well as the worst
5-yr-OS and the lowest 5-yr-DFS were found in the DM patients.
Disclosure Statement: Nothing to be disclosed.
515
Body Mass Index (BMI) Dependent Outcome in Colon
Cancer(CA) Surgery – Interims Results of a Prospective
Multi-Center Observational Study
Romy Kreyer 1; Ronny Otto 2; Hans Lippert 2; Ingo Gastinger 2; Henry Ptok 1;
Roland S. Croner 1; Frank Meyer 1
1Dept. of General, Abdominal, Vascular and Transplant Surgery, University
Hospital at Magdeburg, Magdeburg, Deutschland
2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg, Deutschland
Purpose: To verify the impact of BMI onto immediate post-op. & long-
term oncological outcomes following colon Ca surgery.
Methods: Patients (nTotal=8,574; mean age, 71 [range, 18-98] yrs; sex ratio,
m:f=53.7:46.3%) were classied according to WHO denitions for BMI
into under-/normal-/overweight & obese (<18.5/18.5-24.9/25-29.9/>30
kg/m2, resp.).
Early postop. outcome comprised morbidity & hospital mortality.
Long-term oncological outcome was specically characterized by
5-yr-overall survival (5-yr-OS), 5-yr-disease-free survival (5-yr-DFS) &
5-yr-local recurrence rate (5-yr-LRR).
Results: e relative portions for the BMI categories were as follows:
Under-, 2.1%; normal-, 36.5%; overweight, 40.3% & obese, 21.2%. e
highest progression of the Tu disease was found in the underweight pa-
tients. More advanced Tu stages (according to UICC classication) were
detected in the normal weight group compared to overweight & obese
patients (P<0.001 each). In addition, both underweight & obese patients
showed worse ASA scoring (P<0.001). With a total morbidity of 35%,
obese patients suered most from surgical complications (P<0.001) vs.
underweight category was associated with the highest rate of general
complications aer surgical intervention (P=0.183). e overall in-hos-
pital mortality was 3.7%. Obese subjects had better 5-yr-OS (63.1%) than
normal weight individuals (54.4%; P<0.001). In addition, overweight cas-
es were not dierent compared to obesity (P=0.205). e lowest 5-yr-OS
rates were found in the underweight group of patients (38.9%; P<0.001
- overall 5-yr-OS, 58.8%).With the lowest proportion of local recurrences
(5-yr-LRR, 1.4%), only the obesity category had a signicant inuence on
5-yr-LRR (P<0.016; LRR in total, 2.88%). Despite the higher 5-yr-LRR in
the underweight cases, it was not signicantly dierent (P>0.264).
Conclusions: Results are similar to previously obtained rectal Ca data on
long-term outcome emphasizing the obesity paradox.
Disclosure Statement: Nothing to be disclosed.
516
Multicenter Study Results on Colon Cancer Conducted
by a Single Research Group – an Overview
Frank Meyer 1; Henry Ptok 1; Ralf Steinert 2; Ronny Otto 3; Ingo Gastinger 3;
Hans Lippert 3
1Dept. of General, Abdominal, Vascular and Transplant Surgery, University
Hospital at Magdeburg, Magdeburg, Deutschland
2Dept. of General and Abdominal Surgery, St Josef Hospital at Salzkotten,
Salzkotten, Deutschland
3Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg, Deutschland
Purpose: To summarize results on the surgical management of colon
cancer(Ca), its quality assurance & their consequences for daily surgical
practice.
Methods: Prospective multicenter observational study data on diagnos-
tic, treatment & outcome of patients with colon Ca over a dened study
period.
Results (selective):
1) Case load in general does not provide necessarily a signicant
impact onto the outcome.
2) Age can be considered a risk factor, however, it can not be
considered a contraindication for surgcial treatment of colon Ca.
3) Hartmanns procedure is still indicated in high-risk patients &
emergency cases to reduce morbidity & mortality.
4) Hospital volume does not provide a signicant impact onto the
early postop. outcome.
5) Implantation of self-expanding stents (SEMS) can be considered
an ecient measure in endoscopic palliation of the malignant
colonic stenosis – it reduces postop. complications in bridging of
stenosing tumor growth of colon Ca until surgical intervention.
6) Laparoscopic approach in resection of colon Ca is reasonable
in a well dened portion of patients; it should be performed
by experienced surgeons since conversion to open surgery is
associated with a signicant increase of morbidity, mortality &
hospital stay.
7) Anastomotic insuciency in colon resection is a rare but severe
complication, which is associated with specic risk factors.
Conclusions: e aquisition of such data can provide important hints &
knowledge for future care.
Disclosure Statement: Nothings has to be disclosed.
517
Quality Assurance in Rectal Cancer - Multicenter Study Results
Obtained By One Research Group
Frank Meyer 1; Ralf Steinert 2; Henry Ptok 1; Ronny Otto 3; Hans Lippert 3;
Ingo Gastinger 3
1Dept. of General, Abdominal, Vascular and Transplant Surgery, University
Hospital at Magdeburg, Magdeburg, Deutschland
2Dept. of General and Abdominal Surgery, St Josef Hospital at Salzkotten,
Salzkotten, Deutschland
3Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg, Deutschland
Purpose: To analyze data on diagnostic & treatment prole, outcome as
well as quallity assurance of surgical care in the management of rectal can-
cer(Ca).
Methods: Prospective multicenter observational study (design) in pa-
tients with rectal Ca over a dened study period.
Results:
- Hospital volume did not have a signicant impact onto the oncosur-
gical long-term outcome.
- Neoadjuvant radiochemotherapy did not increase the risk of a
postoperative anastomotic insuciency or dysfunction of the
urinary bladder aer sphincter-preserving rectal resection with
curative intention.
- Creation of a protective enterostoma did not reduce the frequency of
a postop. anastomotic insuciency but it lowered the frequency of
following surgical or interventional consequences.
- Quality of TME depends on patient- & treatment-associated factors.
- Patient’s age is a risk factor but it can not be considered a general
contraindication for resection of rectal Ca.
- Oncological outcome aer laparoscopic rectum resection is compa-
rable with that aer open resection (worsening aer conversion).
- Limited resection of pT1-low-risk carcinoma may provide an accept-
able oncosurgcial outcome.
- Rate of abdominoperineal rectum exstirpation (APR) has been re-
duced in routine surgical care down to approximately 20%.
Conclusions: e results i) reect real situation in abdominal surgery in
Germany, ii) have inuenced disease-specic clincial management, and
iii) may dene novel subjects of up-coming studies.
Disclosure Statement: Nothing to be diosclosed.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts54
Inhalt
2018
Index
2018
543
Colorectal Cancer Screening with Fecal Immunochemical
Tests – The Impact of Anatomical, Morphological and
Histopathological Adenoma Characteristics on Test
Sensitivity: Systematic Review and Meta-Analysis
Jovan Todorovic 1; Beate Jahn 1, 2; Marija Mladenovic 1; Gaby Sroczynski 1;
Ursula Rochau 1; Sibylle Puntscher 1; Jùlia Santamaria 1; Valentino Allende 1;
Slavica Stojnev 3; Uwe Siebert 1, 2, 4, 5
1Institute of Public Health, Medical Decision Making and Health Technology
Assessment, Department of Public Health, Health Services Research and Health
Technology Assessment, UMIT – Private University for Health Sciences, Medical
Informatics and Technology, Hall in Tirol, Österreich
2Division of Health Technology Assessment and Bioinformatics, ONCOTYROL –
Center for Personalized Cancer Medicine, Innsbruck, Österreich
3Department of Pathology, Faculty of Medicine, University of Nis, Niš, Serbia
4Center for Health Decision Science, Department of Health Policy and
Management, Harvard Chan School of Public Health, Boston, MA, USA
5Institute for Technology Assessment and Department of Radiology,
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Purpose: Fecal immunochemical tests (FIT) are recommended for col-
orectal cancer (CRC) screening. Dierent adenoma characteristics can af-
fect FIT sensitivity. We aimed to systematically investigate adenoma char-
acteristics inuencing FIT sensitivity and leading to false-negative results.
Methods: Literature search was conducted in MEDLINE, Cochrane Li-
brary and EMBASE databases. Included studies had to provide quantita-
tive information on FIT sensitivity with regard to dierent specic adeno-
ma characteristics. We limited our search to articles published 2010-2019
in English language. Evidence tables were used to systematically combine
study characteristics. e dierences between sensitivity of distal and
proximal adenomas were pooled using a xed eects meta-analysis model
and 95% condence intervals (CI) were calculated.
Results: 11 studies were included in our review. Study designs varied with
8 prospective and 3 retrospective studies. Identied characteristics leading
to low FIT sensitivity are proximal localization, non-polypoid morphol-
ogy and serrated type. e pooled absolute dierence in FIT sensitivity
between proximal and distal adenomas was 15% (95% CI: 11%-19%). FIT
sensitivity was signicantly lower for at as compared to non-at adeno-
mas (11%). e largest statistically signicant dierence between sessile
serrated (SSA/P) and conventional advanced adenoma was 20%. FIT re-
sults in high proportion of false-negative results (16%) for patients with
proximal and small (≥10 mm) or at adenomas.
Conclusions: Our ndings suggest that localization in the proximal co-
lon, at adenomas and SSA/Ps are the most unfavorable for detection in
early stages when the curative treatment could prevent CRC development.
Imperiale TF, et al. 2019.
Niedemaier T, et al. 2018.
Disclosure Statement: No conict of interest.
569
Integrated Biobanking and Tumor Model Establishment
of Human Colorectal Carcinoma Provides Excellent Tools
for Modern Precision Medicine
Christina Mullins 2; Bianca Micheel 1; Stephanie Matschos 1;
Matthias Leuchter 1; Florian Bürtin 1; Maja Hühns 3; Ernst Klar 1;
Friedrich Prall 3; Michael Linnebacher 1
1Chirurgie, Universitätsmedizin Rostock, Rostock, Deutschland
2Thoraxchirurgie, Universitätsmedizin Rostock, Rostock, Deutschland
3Pathologie, Universitätsmedizin Rostock, Rostock, Deutschland
Purpose: Over the time period from 2006 to 2017, consecutive patients
operated on at the University Medical Center Rostock participated in this
comprehensive biobanking and tumor-modelling approach: the HROC
collection. Samples were collected using strict SOP including blood (se-
rum und lymphocytes), tumor tissue (vital and snap frozen) as well as ad-
jacent normal epithelium. Patient and tumor data including classication,
molecular type, clinical outcome and results of model establishment are
the essential pillars.
Methods: Overall 149 patient-derived xenogras, 34 primary and 35 sec-
ondary cell lines were successfully established and encompass all colorec-
tal carcinoma anatomic sites, grading and staging types and molecular
classes. e HROC collection represents one of the largest model assort-
ments from consecutive clinical CRC cases worldwide.
Results: Statistical analysis identied a variety of clinicopathological and
molecular factors associated with model success in univariate analysis;
several of them not identied before: localization, mutational status of
K-Ras and B-Raf, MSI-status as well as grading and staging parameters.
Surprisingly, in multivariate analysis model success solely correlated pos-
itively with the nodal status N1 and mutations in the genes K-Ras and
B-Raf. ese results imply that generating CRC tumor models on the in-
dividual patient level is worth considering especially for advanced tumor
cases with a dismal prognosis.
Conclusions: In sum, this study succeeded in generating CRC in vitro
and in vivo models from all subtypes of CRC with the exception of FAP.
To the best of our knowledge, the HROC collection represents the largest
single-center integrated biobanking activity of CRC-patient biomateri-
al plus individual-patient-derived in vitro and matching in vivo models
worldwide. Several clinical and molecular factors signicantly inuencing
success of model generation were identied – many for the rst time. All
models are available upon reasonable request.
Disclosure Statement: none to declare
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Inhalt
2018
Index
2018
608
Beacon Crc: a Randomized, Phase 3 Study of Encorafenib
(ENCO) and Cetuximab (CETUX) with or without Binimetinib
(BiNI) vs. Choice of Either Irinotecan or Folri Plus Cetux in
BRAF V600E–Mutant Metastatic Colorectal Cancer (mCRC)
Arndt Vogel 1; Susanna Hegewisch-Becker 2; Gerald Prager 3;
Gunnar Folprecht 4; Michael Stahl 5; Scott Kopetz 6; Axel Grothey 7;
Eric van Cutsem 8; Rona Yaeger 9; Harpreet Wasan 10; Takayuki Yoshino 11;
Jayesh Desai 12; Fortunato Ciardello 13; Ashwin Gollerkeri 14; Kati Maharry 14;
Fotios Loupakis 15; Hong Y 16; Neeltje Steeghs 17; Tormod Kyrre Guren 18;
Hendrik-Tobias Arkenau 19; Pilar García-Alfons 20; Victor Sandor 14;
Janna Christy-Bittel 21; Lisa Anderson 14; Josep Tabernero 22
1Gastroenterology, Hepatology and Endocrinology, Hannover Medical School,
Hannover, Deutschland
2HOPE-Practice for Oncology, Hamburg, Deutschland
3Department of Medicine, Medical University of Vienna, Vienna, Österreich
4University Clinic Dresden, Oncology Department, Dresden, Deutschland
5Department of Medical Oncology and Hematology, Evang. Kliniken Essen-
Mitte, Essen, Deutschland
6UT MD Anderson Cancer Center, Houston, TX, United States
7Mayo Clinic, Rochester, Minnesota, United States
8UZ Leuven-Campus Gasthuisberg, Leuven, Belgien
9Memorial Sloan-Kettering Cancer Center, New York, NY, United States
10Hammersmith Hospital, Department of Cancer Medicine, London, United
Kingdom
11Department of Gastroenterology and Gastrointestinal Oncology, National
Cancer Hospital East, Kashiwa, Japan
12Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Walter and
Aliza Hall Institute, Parkville, VIC, Australien
13Università degli Studi della Campania L., Dipartimento di Medicina di
Precisione, Napoli, Italien
14Array BioPharma Inc, Boulder, CO, United States
15Medical Oncology Unit 1, Clinical and Experimental Oncology Department,
Veneto Institute of Oncology IOV-IRCCS, Padua, Italien
16Asan Medical Center, Seoul KR, Seoul, Südkorea
17Netherlands Cancer Institute, Amsterdam, Niederlande
18Oslo University Hospital, Oslo, Norwegen
19Sarah Cannon Research Institute, HCA Healthcare, London, United Kingdom
20Medical Oncology Department. Hospital General Universitario Gregorio
Marañón, Madrid, Spanien
21Array BioPharma Inc, Cambridge, MA, United States
22Vall d’Hebron University Hospital, Barcelona, Spanien
Purpose: BRAF V600E mutations are identied in up to 15% of mCRC
patients (pts) and confer a poor prognosis. Objective response rates
(ORR) to chemotherapy in ≥ 2 line are generally less than 10%, with me-
dian progression-free survival (PFS) and overall survival (OS) of approx-
imately 2 and 4-6 months, respectively. A 30-patient safety lead-in with
ENCO+BINI+CETUX showed acceptable safety and encouraging activity
in these pts.
Methods: e BEACON CRC Study (NCT02928224) was a multicenter,
randomized, open-label, phase 3 study to evaluate ENCO+CETUX with/
without BINI (triplet or doublet) vs. choice of irinotecan or FOLFIRI +
CETUX (control) in pts with BRAF V600E‒mutant mCRC who had pro-
gressed aer 1 or 2 prior palliative regimens. e primary endpoints were
OS and ORR (by blinded central review) comparing triplet to control arm;
secondary end points included OS for the doublet arm as well as PFS and
safety.
Results: 665 pts were randomly assigned to the triplet (n = 224), doublet
(n = 220), or control arm (n = 221). Median OS was 9.0 months (95% CI,
8.0-11.4) for the triplet and 5.4 months (95% CI, 4.8-6.6) for the control
regimen (HR, 0.52; 95% CI, 0.39-0.70, p < .0001). Conrmed ORR of the
triplet was 26% and 2% for the control (p < .0001). Median OS for the
doublet combination was 8.4 months (95% CI, 7.5-11.0) (HR vs. control,
0.60; 95% CI, 0.45-0.79; P = .0003). Adverse events were as anticipated
based on prior trials with each combination. Grade 3 or 4 adverse events
were seen in 58%, 50% and 61% of pts in the triplet, doublet and control
arm, respectively.
Conclusions: ENCO+BINI+CETUX improved OS and ORR in pts with
BRAF V600E-mutant mCRC when compared with current standard of
care chemotherapy and had a safety prole consistent with the known
safety prole of each agent. is targeted therapy regimen should be a
new standard of care for this patient population.
e study was published at ESMO World GI congress 2019.
Conicts of Interest: AV: honoraria from Pierre Fabre.; GP: speaker, advisory
board member, other type of consultant: Celgene, Bayer, Roche, Shire, Halozyme,
Lilly, BMS, Pierre Fabre, Amgen, Servier, MSD, Merck, Taiho; GF: honoraria from
Merck, Roche, Sano-Aventis, Lilly, Bayer, Servier, Mundipharma, BMS, MSD;
Research funding: Merck; SK: Stock and Other Ownership Interests: Molecular-
Match, Navire Consulting or Advisory Role: Roche, Genentech, EMD Serono,
Merck, Karyopharm erapeutics, Amal erapeutics, Navire Pharma, Sympho-
gen, Holy Stone, Biocartis, Amal erapeutics, Amgen, Novartis, Eli Lilly, Boeh-
ringer Ingelheim; AG: Honoraria: Elsevier, Aptitude Health Consulting or Adviso-
ry Role: Genentech (Inst), Bayer (Inst), Bristol-Myers Squibb (Inst), Eli Lilly (Inst),
Boston Biomedical (Inst), Amgen (Inst), Array BioPharma (Inst), Guardant Health
(Inst), Daiichi Sankyo (Inst), Research Funding: Genentech (Inst), Bayer (Inst),
Pzer (Inst), Eisai (Inst), Eli Lilly (Inst), Boston Biomedical (Inst), Daiichi Sankyo
(Inst), Array BioPharma (Inst); Travel, Accommodations, Expenses: Genentech,
Bayer, Bristol-Myers Squibb, Boston Biomedical, Amgen, Boehringer Ingelheim,
Merck Sharp & Dohme; EVC: Consulting or Advisory Role: Bayer, Eli Lilly, Roche,
Servier, Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, Merck KGaA,
Novartis, AstraZeneca; Research Funding: Amgen (Inst), Bayer (Inst), Boehringer
Ingelheim (Inst), Eli Lilly (Inst), Novartis (Inst), Roche (Inst), Celgene (Inst),
Ipsen (Inst), Merck (Inst), Merck KGaA (Inst), Servier (Inst), Bristol-Myers Squibb
(Inst); RY: Research Funding: Array BioPharma, GlaxoSmithKline, Novartis;
Travel, Accommodations, Expenses: Array BioPharma; Speakers’ Bureau: Sysmex;
Research Funding: Symphogen; Patents, Royalties, Other Intellectual Property:
Patent licensed by Biocartis (Inst); HW: Honoraria: Merck KGaA, Celgene, Sirtex
Medical, Servier, Array BioPharma, Shire, Genentech, ERYTECH Pharma; Con-
sulting or Advisory Role: Roche Pharma AG, SITEX Medical, ERYTECH Pharma,
Shire, Incyte; Speakers’ Bureau: Sirtex Medical, Celgene, Merck KGaA, Servier;
Research Funding: Sirtex Medical (Inst), Merck KGaA (Inst), Pzer (Inst), Merck
Sharp & Dohme (Inst); TY: Research Funding: Chugai Pharma (Inst), Sano (Inst),
Sumitomo Dainippon (Inst), GlaxoSmithKline (Inst); JD: Consulting or Advisory
Role: Bionomics, Eli Lilly, Eisai, BeiGene, Ignyta (Inst); Research Funding: Roche
(Inst), GlaxoSmithKline (Inst), Novartis (Inst), Bionomics (Inst), MedImmune
(Inst), BeiGene (Inst), Eli Lilly (Inst), Bristol-Myers Squibb (Inst); FC: Consult-
ing or Advisory Role: Genentech, Merck KGaA, Bayer, Amgen, Pzer; Research
Funding: Merck KGaA (Inst), Genentech (Inst), Servier (Inst), Symphogen (Inst),
Amgen (Inst), Bayer (Inst), Merck Sharp & Dohme (Inst), Bristol-Myers Squibb
(Inst), Ipsen (Inst); AG: Employment: Array BioPharma, Alnylam (I), Bluebird Bio
(I); Stock and Other Ownership Interests: Array BioPharma, Alnylam (I); Hon-
oraria: Bluebird Bio (I); Patents, Royalties, Other Intellectual Property: Receives
royalties from Yale University on an antibody used in nephrology basic research
(I); KM: Employment: Array BioPharma; Stock and Other Ownership Interests:
Array BioPharma; Travel, Accommodations, Expenses: Array BioPharma; NS:
Research funding (inst): ompany: AstraZeneca/MedImmune, Bayer, Bristol-Myers
Squibb, Novartis, GlaxoSmithKline, Pzer, Roche, Genentech/Roche, Boehringer
Ingelheim, Blueprint Medicines, AB Science, Deciphera, Blueprint Medicines,
Genentech, Merck Sharp & Dohme, Amgen, Merus, Lilly, Incyte; VS: Employment:
Array BioPharma; Leadership: Array BioPharma; Stock and Other Ownership
Interests: Array BioPharma; JCB: Employment: Array Biopharma; Stock and Other
Ownership Interests: Array Biopharma, Gilead Sciences; LA: Array employee;
Employment: Array BioPharma; Stock and Other Ownership Interests: Array
BioPharma; Travel, Accommodations, Expenses: Array BioPharma; JT: Consulting
or Advisory Role: Bayer, Boehringer Ingelheim, Eli Lilly, MSD, Merck Serono,
Novartis, Sano, Taiho Pharmaceutical, Merrimack, Peptomyc, Rafael Pharmaceu-
ticals, Symphogen, Chugai Pharma, Ipsen, Merus, Pzer, Seattle Genetics, Array
BioPharma, AstraZeneca, BeiGene, Genentech, Genmab, Halozyme, Imugene
Limited, Inection Biosciences Limited, Kura, Menarini, Molecular Partners,
Pharmacyclics, ProteoDesign SL, Roche, Seattle Genetics, Servier, VCN Bioscienc-
es, Biocartis, Foundation Medicine, HalioDX SAS, Roche Diagnostics; FT, YH, TG,
TA, PGA have nothing to dislose.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts56
Inhalt
2018
Index
2018
627
Are Visceral Obesity and Sarcopenia Postoperative Risk
Factors for Patients Undergoing Hepatic Resections for
Synchronous Colorectal Liver Metastases?
Mira Runkel 1; Thierno Diallo 2; Fabian Bamberg 2; Stefan Fichtner-Feigl 1;
Sven A. Lang 1
1Universitätsklinikum Freiburg, Klinik für Allgemein-und Viszeralchirurgie ,
Freiburg im Breisgau, Deutschland
2Universitätsklinikum Freiburg, Klinik für Radiologie , Freiburg im Breisgau,
Deutschland
Purpose: e impact of body fat composition on surgical outcomes is
controversial. is study examined whether sarcopenia or visceral obesi-
ty were risk factors aer hepatic resection of synchronous colorectal liver
metastases.
Methods: 94 consecutive patients with primary hepatic resections for syn-
chronous colorectal metastases were identied from a single cancer center
database between January 2013 and August 2018. Body fat distribution
and sarcopenia were retrospectively calculated from single-slice CT im-
ages at the level of L3.
Results: 63,8% (n=60) of patients had postoperative complications, where-
as only 18,1% (n=17) had major complications (Clavien-Dindo grade IIIb
and above). 36,2 % (n=34) of patients had sarcopenia and 70,2% (n=66)
were viscerally obese. Dierent denitions for visceral obesity included
visceral fat area (VFA) > 100cm², VFA >168cm² for men and >80 cm² for
women and visceral to subcutaneous fat ratio (V/S) >0,4. All denitions
of visceral obesity showed a signicant impact on postoperative compli-
cations (p=0,002, p=0,014, p=0,015, respectively). Higher grades of com-
plications were observed with viscerally obese patients (p=0,002). BMI
was not a predictor for postoperative outcomes (p=1,0). Sarcopenia was
not signicantly associated with postoperative complications (p=0,461),
however, it was shown to increase the length of hospital stay (p=0,028).
Neither sarcopenia nor visceral obesity had an impact on overall survival.
Conclusions: Visceral obesity but not sarcopenia correlates with short-
term postoperative outcomes aer hepatic resections and may thus serve
for better preoperative risk stratication.
Disclosure Statement: No Disclosures.
661
Beyond Proximal or Distal Location: Colonoscopy and
Reduction of Colorectal Cancer Risk By Molecular Subtypes
and Pathways
Michael Homeister 1; Hendrik Bläker 2; Lina Jansen 1; Elizabeth Alwers 1;
Efrat Amitay 1; Prudence Carr 1; Matthias Kloor 3; Esther Herpel 3;
Wilfried Roth 4; Jenny Chang-Claude 1; Hermann Brenner 1
1Klinische Epidemiologie und Alternsforschung, Deutsches
Krebsforschungszentrum, Heidelberg, Deutschland
2Institut für Pathologie, Universitätsmedizin Leipzig, Leipzig
3Institut für Pathologie, Universitätsklinik Heidelberg, Heidelberg
4Institut für Pathologie, Universitätsmedizin Mainz, Mainz
Purpose: In previous studies, the protective eect of colonoscopy was
generally stronger for distal than for proximal colorectal cancer (CRC)
(1,2). is study aimed to investigate whether the association of colonos-
copy and CRC risk varies according to major molecular pathological fea-
tures and pathways of CRC.
Methods: Population-based case-control study from Germany, including
2132 patients with a rst diagnosis of CRC and information on major
molecular tumor markers, and 2486 control participants without CRC.
Detailed participant characteristics were collected by standardized ques-
tionnaires and information on previous colonoscopy was derived from
medical records.
Results: Overall, we observed strong risk reduction of CRC aer colonos-
copy that was weaker for microsatellite instable (MSI) than for non-MSI
CRC (p for heterogeneity <0.0001), for CpG island methylator phenotype
(CIMP) high CRC than for CIMP low/negative CRC (p het=0.0011), for
BRAF-mutated than for BRAF non-mutated CRC (p het <0.0001), for
KRAS non-mutated than for KRAS-mutated CRC (p het=0.0415), and
for CRC classied into the sessile serrated pathway than for CRC of the
traditional pathway (p het=0.0009). Aer colonoscopy with detection of
adenomas, no risk reduction was found for sessile serrated pathway CRC.
Conclusions: Our study extends the molecular understanding of existing
dierences in risk reduction of proximal and distal CRC reported by pre-
vious studies, and may imply relevant information for improving strate-
gies for timely detection of relevant precursors.
References:
1. Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, et al. Long-
term colorectal-cancer incidence and mortality aer lower endoscopy. N Engl
J Med. 2013:1095-105.
2. Brenner H, Chang-Claude J, Jansen L, Knebel P, Stock C, Homeister M.
Reduced risk of colorectal cancer up to 10 years aer screening, surveillance,
or diagnostic colonoscopy. Gastroenterology. 2014:709-17.
Disclosure Statement: e authors declare that they have no conict of interest.
688
Utilization of Repeat Colonoscopies and Polypectomies
in Germany within 10 Years: a Claims Data Analysis Based
on More Than 2 Million Index Colonoscopies
Sarina Schwarz 1; Ulrike Haug 1, 2
1Leibniz-Institut für Präventionsforschung und Epidemiologie - BIPS, Bremen,
Deutschland
2Fachbereich 11 der Universität Bremen: Human- und
Gesundheitswissenschaften
Purpose: In Germany, >6 million colonoscopies are performed per year,
but longer-term follow-up data to monitor colonoscopy use at the indi-
vidual level are lacking. We aimed to explore the potential of German
claims data to describe the utilization and the diagnostic yield of repeat
colonoscopy.
Methods: We used the German Pharmacoepidemiological Research Da-
tabase (GePaRD), containing claims data with information on ~25 mil-
lion persons, to identify patients who underwent at least one colonoscopy
between 2006 and 2015. We only included persons with ≥2 years of con-
tinuous health insurance before the index colonoscopy. We excluded all
patients with a diagnosis code for colorectal cancer within 2 years before
index colonoscopy. We dened 3 sub-cohorts according to procedure/
diagnosis codes at index colonoscopy: Patients with a code for snare pol-
ypectomy (cohort 1), patients with no snare polypectomy but a diagnosis
code for polyps (cohort 2) and patients without such codes (cohort 3). We
described the sub-cohorts regarding utilization of and snare polypecto-
mies performed at repeat colonoscopy. All analyses were stratied by type
of index colonoscopy (diagnostic vs. screening).
Results: Overall, 2,520,445 persons with at least one colonoscopy were
included (cohort 1: 15%; cohort 2: 14%; cohort 3: 71%). e proportions
of persons entering cohorts with a screening colonoscopy were 47%, 39%
and 35%, respectively. Among these, the proportions with at least one re-
peat colonoscopy in cohort 1, 2 and 3 were 70%, 59% and 36%, and a
snare polypectomy at rst repeat colonoscopy was performed in 30%, 15%
and 10%, respectively. Among persons entering cohorts with a diagnostic
colonoscopy, the proportions with at least one repeat colonoscopy were
71%, 66% and 48%, and a snare polypectomy at rst repeat colonoscopy
was performed in 32%, 14% and 8% of these, respectively.
Conclusions: Claims data can provide useful information on utilization
of repeat colonoscopy in Germany and – although histological data are
lacking – provide an estimate on polyp detection.
Disclosure Statement: None.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 57
Inhalt
2018
Index
2018
704
KRAS Mutation Status Concordance Between the Primary Tumor
and the Corresponding Metastasis in Patients with Rectal Cancer
Peter Jo 1; Markus Bernhardt 1; Manuel Nietert 2; Alexander König 3;
Azadeh Azizian 1; Markus Schirmer 4; Marian Grade 1; Julia Kitz 5;
Michael Ghadimi 1; Philipp Ströbel 5; Hans-Ulrich Schildhaus 6;
Jochen Gaedcke 1
1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und
Kinderchirurgie, Göttingen, Deutschland
2Universitätsmedizin Göttingen, Abteilung für Medizinische Statistik
3Universitätsmedizin Göttingen, Klinik für Gastroenterologie und
gastrointestinale Onkologie
4Universitätsmedizin Göttingen, Abteilung für Strahlentherapie und
Strahlenonkologie
5Universitätsmedizin Göttingen, Abteilung für Pathologie
6Universitätsmedizin Duisburg-Essen, Abteilung für Pathologie
Purpose: KRAS is a negative predictive indicator for EGFR-treatment-
response in patients with colorectal cancer. We have shown KRAS mutation
status concordance in patients with locally advanced rectal cancer treated
preoperatively indicating no relevant heterogeneity within and between
multiple pre- and posttherapeutic samples of the primary tumor. e aim of
this study was to evaluate the heterogeneity of KRAS mutation status between
the primary tumor and the corresponding metastasis in the same collective
and to evaluate the ideal representative tissue for KRAS mutation testing.
Methods: KRAS mutation status analyses were performed in a previous
study from 47 patients with rectal cancer to evaluate the intratumoral het-
erogeneity. In this study 6 patients were excluded due to missing follow up
data. 15 patients showed recurrence during the follow up. DNA from rep-
resentative areas of metastatic tissue was obtained from FFPE specimens
from 11 metastatic rectal cancer patients. Mutations in KRAS codons 12,
13, and 61 were analyzed by the therascreen® KRAS test.
Results: e mean age was 64.13 ± 10.64 years. 19 patients showed a KRAS
mutation. Of the 11 patients with a metastatic disease or local recurrence, 5
patients showed a KRAS mutation. A signicant KRAS mutation status con-
cordance was detected in 81.18% (9/11) of the patients (p=0.03271). Only 2
patients showed intertumoral heterogeneity, which harbored in one patient
a KRAS G12C mutation status in the primary tumor, but a G12V KRAS
mutation status in the corresponding lung lesion, and in the other patient
a G12A mutation in the primary lesion and a WT in the lung metastasis.
Conclusions: We show a signicant concordance of the KRAS mutation
status between tumor samples obtained from the primary tumor and the
metastasis in patients with rectal cancer indicating no relevant intertumoral
heterogeneity. Our data suggest that sampling either the primary or meta-
static lesion is valid for the initial evaluation of KRAS mutation status pre-
dicting the response to anti-EGFR treatment and guiding clinical decisions.
812
Epigenome Mapping Identies Tumor-Specic Gene
Expression in Primary Rectal Cancer
Hannah Flebbe 1; Feda H. Hamdan 1, 2; Vijayalakshmi Kari 1; Julia Kitz 3;
Jochen Gaedcke 1; B. Michael Ghadimi 1; Steven A. Johnsen 2;
Marian Grade 1
1Department of General, Visceral and Pediatric Surgery, University Medical
Center Goettingen, Göttingen, Deutschland
2Gene Regulatory Mechanisms and Molecular Epigenetics Laboratory, Division
of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States
3Institute of Pathology, University Medical Center Goettingen, Göttingen,
Deutschland
Purpose: Epigenetic alterations play a central role in cancer development
and progression (1). e acetylation of histone 3 at lysine 27 (H3K27ac)
specically marks active genes (2). While chromatin immunoprecipita-
tion (ChIP) followed by next-generation sequencing (ChIP-seq) analyses
are commonly performed in cell lines, only limited data are available from
primary tumors. We therefore examined whether cancer-specic alter-
ations in H3K27ac occupancy can be identied in primary rectal cancer
Methods: Tissue samples from primary rectal cancer and matched mucosa
were obtained. ChIP-seq for H3K27ac was performed and dierentially oc-
cupied regions were identied. e expression of selected genes displaying
dierential occupancy between tumor and mucosa were examined in gene
expression data from an independent patient cohort. Dierential expression
of four proteins was further examined by immunohistochemistry.
Results: ChIP-seq for H3K27ac in primary rectal cancer and matched mu-
cosa was successfully performed and revealed dierential binding on 44
regions. is led to the identication of genes with increased H3K27ac, i.e.,
RIPK2, FOXQ1, KRT23, and EPHX4, which were also highly upregulated
in primary rectal cancer in an independent dataset. e increased expres-
sion of these four proteins was conrmed by immunohistochemistry.
Conclusions: is study demonstrates the feasibility of ChIP-seq-based
epigenome mapping of primary rectal cancer and conrms the value of
H3K27ac occupancy to predict gene expression dierences.
References:
1. Markowitz, S.D.; Bertagnolli, M.M. Molecular origins of cancer: Molecular
basis of colorectal cancer. N. Engl. J. Med. 2009, 361, 2449-2460.
2. Rickels, R.; Shilatifard, A. Enhancer Logic and Mechanics in Development and
Disease. Trends Cell Biol. 2018, 28, 608–630
Disclosure Statement: Data has recently been published:
Flebbe, H.; et al. Epigenome Mapping Identies Tumor-Specic Gene Expression
in Primary Rectal Cancer. Cancers 2019; 11(8);1142.
830
Therapy-Dependent Survival in Patients with Colorectal
Peritoneal Carcinomatosis - a Population-Based Study
Patricia Hauer 1; Mareike Mischke 1; Marlene Kaltenstadler 1;
Michael Gerken 2; Pompiliu Piso 3; Monika Klinkhammer-Schalke 2;
Hans Schlitt 1; Matthias Hornung 1
1Klinik und Poliklinik für Chirurgie, Uniklinik Regensburg, Regensburg,
Deutschland
2Tumorzentrum Regensburg, Regensburg, Deutschland
3Klinik für Allgemein- und Viszeralchirurgie, Krankenhaus Barmherzige Brüder
Regensburg, Regensburg, Deutschland
Purpose: Various studies showed a signicant survival benet for cytore-
ductive surgery (CRS) with HIPEC (hyperthermic intraperitoneal chemo-
therapy) compared to surgery and systemic chemotherapy in patients with
peritoneal carcinomatosis (PC). However, a recent prospective randomized
study reported no superiority of CRS and HIPEC to CRS with chemother-
apy, so that now, independent of the CRS, the eectiveness of HIPEC is un-
clear. e aim of this multicenter, retrospective cohort study was the anal-
ysis of treatment-dependent overall survival (OS) aer CRS with HIPEC
compared to surgery and subsequent chemotherapy in patients with PC.
Methods: Based on the clinical cancer registry of the Regensburg Tumor
Center, a retrospective, multicenter cohort study was performed on 941
patients diagnosed with colorectal PC between 2004 and 2018. Primary
endpoint was the therapy-dependent OS estimated using Kaplan-Mei-
er method and multivariable Cox-regression. Risk adjustment was per-
formed for age, sex, primary tumor stage and localization, extraperitoneal
tumor spread, syn- and metachronous PC.
Results: In the included 941 cases, 63 cases were treated with CRS and HIPEC
(6.7%), 176 cases (18.7%) with surgery followed by chemotherapy. Median OS
aer CRS and HIPEC was 40.5 months, aer surgery with chemotherapy 21.4
months. Two-year OS aer CRS and HIPEC was 58.2% (surgery with chemo-
therapy 41.8%); 3-year OS 50.1% and 21.4%, resp. (log rank p<0.001). Aer
risk adjustment, CRS and HIPEC persisted to prove superior to surgery with
chemotherapy (HR 0.529, CI 95% 0.363-0.770, p<0.001). In addition, signi-
cant factors inuencing OS were age, tumor histology and grading, presence
of extraperitoneal metastases, T and N status, onset of PC.
Conclusions: In line with most randomized and retrospective studies to
date, this population-based analysis shows a signicant survival benet of
CRS with HIPEC versus surgery and subsequent chemotherapy.
Disclosure Statement: no conict of interests
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts58
Inhalt
2018
Index
2018
Gastrointestinal (Noncolorectal) Cancer
Best-of-Abstract-Vorträge
218
FOLFiRI Plus Ramucirumab Versus Paclitaxel Plus
Ramucirumab for Patients with Advanced or Metastatic
Adenocarcinoma of The Stomach or Gastroesophageal
Junction As Second-Line Therapy – Interim Safety and Ecacy
Results from The Phase II Ramiris Study (AIO-STO-0415) of the
German Gastric Group at AIO
Sylvie Lorenzen 1; Peter Thuss-Patience 2; Claudia Pauligk 3; Eray Gökkurt 4;
Thomas J. Ettrich 5; Florian Lordick 6; Michael Stahl 7; Peter Reichardt 8;
Martin Sökler 9; Daniel Pink 10; Stephan Probst 11; Hana Algül 1; Axel Hinke 12;
Thorsten Götze 3; Salah-Eddin Al-Batran 3
1Klinikum rechts der Isar der TU München, München, Deutschland
2Charité-Universitätsmedizin Berlin, Medizinische Klinik m.S. Hämatologie,
Onkologie und Tumorimmunologie, Berlin, Deutschland
3University Cancer Center Frankfurt, Institut für Klinisch-Onkologische
Forschung and IKF Klinische Krebsforschung GmbH am Krankenhaus Nordwest,
Frankfurt/Main, Deutschland
4Hämatologisch-Onkologische Praxis Eppendorf (HOPE), Facharztzentrum
Eppendorf, Hamburg, Deutschland
5Ulm University Hospital, Ulm, Deutschland
6University Cancer Center Leipzig, Leipzig, Deutschland
7Kliniken Essen-Mitte, Essen, Deutschland
8HELIOS Klinikum Berlin-Buch, Berlin, Deutschland
9University Hospital, Tübingen, Deutschland
10Helios Klinikum Bad Saarow, Bad Saarow, Deutschland
11Klinikum Bielefeld, Bielefeld, Deutschland
12CCRC, Düsseldorf, Deutschland
Purpose: Ramucirumab as monotherapy and in combination with pacl-
itaxel is a proven second-line option for advanced gastroesophageal ad-
enocarcinoma (GEA). More and more patients (pts) are pretreated with
docetaxel in the perioperative or rst-line setting. For those pts, the bene-
t of a combination of ramucirumab and paclitaxel is unclear, and physi-
cians would choose an irinotecan-based regimen as second line treatment.
is provides a rationale for the evaluation of FOLFIRI + ramucirumab.
Methods: is is a multicenter, randomized, investigator initiated, phase
II trial, planned to include 111 pts with advanced GEA to receive 2:1 ei-
ther FOLFIRI plus ramucirumab every two weeks (Arm A) or paclitaxel
(days 1, 8, 15 of a 28-day cycle) plus ramucirumab every two weeks (Arm
B). Primary endpoint is 6-months OS rate. is abstract displays inter-
im results of safety and overall objective response (ORR) in docetaxel
pre-treated group from up to 65 randomized pts. e results were needed
to decide on conducting a subsequent phase III study.
Results: 58 (A, 36; B, 22) pts were included in the safety analysis and
50 pts with tumor assessment in the response analysis. Main ≥ grade 3
adverse events were respectively in arms A/B: neutropenia (20%/22%),
fatigue (6%/0%), diarrhea (8%/3%), and related SAEs (14% v 23%). Twen-
ty-nine of 50 pts (58%) were pre-treated with docetaxel. In these pts, ORR
was 30% in Arm A (5/17) and 8% (1/12) in Arm B. Disease control rate
(DCR) was 65% and 50% for Arm A and B respectively.
Conclusions: e interim safety analysis of the RAMIRIS trial has demon-
strated feasibility of the combination of FOLFIRI and ramucirumab.
Docetaxel pre-treated pts had higher ORR and DCR when ramucirumab
is combined with FOLFIRI, instead of paclitaxel.
455
Pancreatic Tumor Remission in PDX-Models By Treatment
with Gemcitabine in Combination with The Oxathiazine 
GP-2250
Britta Majchrzak-Stiller 1; Marie Buchholz 1; Stefan Hahn 2;
Chris Braumann 1; Waldemar Uhl 1
1Allgemein-u Viszeralchirurgie, St.Josef Hospital Bochum, Bochum, Deutschland
2Ruhr Universität Bochum, ABTEILUNG FÜR MOLEKULARE
GASTROENTEROLOGISCHE ONKOLOGIE, Bochum, Deutschland
Purpose: e oxathiazine GP-2250, a newly dened anti-tumor agent,
displays anti-neoplastic activity on pancreatic cancer tissue as shown both
in cell culture in vitro and in patient derived xenogra (PDX) models in
vivo (1). In the present study, GP-2250 was tested in PDX models in com-
bination with the standard chemotherapeutic agent gemcitabine in view
of a potential antineoplastic synergy of the combination treatment in vivo.
Methods: Using nine dierent PDX models of pancreatic cancer, tumors
were grown up to a size of 200 mm³ in nude mice [NMRI-Fox1 nu/nu]
prior to treatment with 500 mg/kg*BW substance GP-2250 three times a
week and twice a week with 50 mg/kg*BW gemcitabine either alone or in
combination for up to 60 days.
Results: While gemcitabine and GP-2250, given as monotherapy, showed
only a limited antineoplastic response, the combination treatment of
gemcitabine with substance GP-2250 resulted in a signicantly higher
antineoplastic activity than gemcitabine or GP-2250 monotherapy. Eight
out of nine tumors showed a response towards this combination treat-
ment. e tumor growth in ve out of the nine PDX models treated with
the drug combination was characterized by a partial remission via RE-
CIST criteria. ree of the remaining PDX models showed an outcome
of stable disease. Remarkably, in one PDX model, which was immediately
resistant to gemcitabine, the combination therapy nevertheless achieved
a reduction in the tumor growth rate which exceeded that of GP-2250
monotherapy.
Conclusions: e partial remission of pancreatic cancer tumor growth
in mice, which was achieved by the combination of gemcitabine with
GP-2250, is strongly relevant towards clinical practice providing a new
therapeutic strategy in pancreatic cancer treatment. ese results provide
the basis for initial clinical studies with this promising combination of
gemcitabine and GP-2250.
Reference:
1. M. Buchholz et al. Innovative substance 2250 as a highly promising anti-
neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo; BMC
Cancer. 2017 Mar 24; 17(1):216. doi: 10.1186/s12885-017-3204-x
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2018
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2018
Vorträge
802
Classication of Barrett’s Carcinoma Specimens by
Hyperspectral Imaging (HSI)
René Thieme 1; Marianne Maktabi 2; Yannis Wichmann 1;
Thomas Neumuth 2; Andreas Melzer 2; Boris Jansen-Winkeln 1;
Claire Chalopin 2; Ines Gockel 1
1Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-,
Transplantations-, Thorax- und Gefäßchirurgie
2Universität Leipzig, Innovation Center Computer Assisted Surgery (ICCAS)
Purpose: Hyperspectral imaging (HSI) technology combines imaging
with spectroscopy and can be used for the classication of malignant and
non-malignant cells. ereby HSI combined with articial intelligent
algorithms can be used to predict tumor cells in in Barretts carcinoma
specimens.
Methods: HSI imaging records light between the visual and near-infra-
red light (500-1000nm). For a rst feasibility study, this technique was
used to discriminate between squamous epithelium and esophageal ad-
enocarcinoma and 45 specimens from Barretts carcinoma patients were
recorded. In 22 of the 45 investigated specimens contained also squamous
epithelium. e specimens were xed routinely aer resection in parafor-
maldehyde, were sliced to 3µm, and were stained by haematoxylin and eo-
sin (HE). A non-parametric supervised classication learning algorithm
(K-nearest neighbours (k-NN)) was used for discrimination.
Results: Barretts adenocarcinoma cells were recorded by HSI in all 45 in-
vestigated cases. Squamous epithelium and Barretts adenocarcinoma cells
displayed dierences in the absorbance between the wave lengths of 500
to 700 nm. For both, the squamous epithelium and the Barretts adenocar-
cinoma cells, the intra group variances of the investigated specimens were
quite low. 333,275 and 74,000 spectra could be measured from Barretts
adenocarcinoma and from squamous epithelium, respectively. Specicity,
sensitivity and precision with a k-NN (k=5) classier were 0.74, 0.92 and
0.94 for the presence of Barrett’s adenocarcinoma cells.
Conclusions: HE-stained squamous epithelium and Barrett’s adeno-
carcinoma cells showed specic spectral alterations, when measured by
HSI. ese characteristics could be used in the future to develop a com-
puter-assisted algorithm to discriminate semi-automated for tumor cells
Barretts carcinoma specimens, which will help to foster decision-making
support in histopathological diagnosis.
Disclosure Statement: None
Poster
117
Alpha Fetoprotein (AFP) Response and Ecacy Outcomes in
the Phase 3 Celestial Trial of Cabozantinib (C) Versus Placebo
(P) in Advanced Hepatocellular Carcinoma (HCC)
Oliver Waidmann 1; R.K. Kelley 2; L. Rimassa 3; B.-Y. Ryoo 4; J.-F. Blanc 5;
S.L. Chan 6; V. Zagonel 7; T. Yau 8; S. Sen 9; D.W. Markby 9; R. Kaldate 9;
A.B. El-Khoueiry 10
1Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland
2UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco,
United States
3Humanitas Research Hospital, Milano, Italien
4Asan Medical Center University of Ulsan College of medicine, Seoul, Südkorea
5Hospital Haut Leveque, Pessac, Frankreich
6Prince of Wales Hospital Shatin, Hong Kong
7Istituto di Ricovero Cura a Carattere Scientico Istituto Oncologico Veneto,
Padova, Italien
8Queen Mary Hospital, Hong Kong
9Exelixis Inc, South San Francisco, United States
10USC Norris Comprehensive Cancer Center, Los Angeles, United States
Purpose: AFP response, dened as a decrease in serum levels of the tu-
mor marker AFP aer therapy, has been associated with improved sur-
vival of patients (pts) with HCC treated with locoregional therapy; high
baseline (b) AFP levels are associated with poor prognosis. In the phase 3
CELESTIAL trial (NCT01908426), C signicantly improved overall sur-
vival (OS) and progression-free survival (PFS) vs P in pts with previously
treated advanced HCC. Here we evaluate clinical outcomes with C in the
CELESTIAL trial based on AFP response or progression on treatment.
Methods: 707 pts were randomized 2:1 to receive C (60 mg qd) or P. El-
igible patients had a pathologic diagnosis of HCC, Child-Pugh score A,
and ECOG PS ≤1. Pts received prior sorafenib and up to 2 lines of prior
systemic therapy for HCC. Serum AFP levels were measured centrally at
b and every 8 weeks thereaer. Outcomes were evaluated for pts with ele-
vated b serum AFP (≥20 ng/mL) based on AFP response (≥20% decrease
from b) or progression (≥20% increase from b) at week 8.
Results: Overall, 331 pts (70%) in the C arm and 160 (68%) in the P arm
had elevated b AFP levels, and 236 (50%) and 111 (47%), respectively,
were evaluable for AFP response at Week 8. Among evaluable pts, 117 pts
(50%) in the C arm vs 14 (13%) in the P arm had an AFP response and 72
(31%) vs 75 (68%), respectively, had AFP progression. Median OS with C
was 16.1 mo for AFP responders vs 9.1 mo for non-responders (HR 0.61,
95% CI 0.45-0.83), and median PFS with C was 7.3 mo vs 4.0 mo (HR
0.55, 95% CI 0.41-0.75). For pts with AFP progression, median OS with C
was 8.1 mo, and median PFS with C was 3.6 mo. Hazard ratios for OS and
PFS with C also favored AFP responders over non-responders when ana-
lyzed according to best response through week 24 or using 50% decrease
from b as the cuto for response.
Conclusions: AFP response rate was higher with C vs P, and AFP response
was associated with longer OS and PFS with C for pts with previously
treated advanced HCC. Response assessment in HCC may be improved
by evaluating on-treatment AFP changes in addition to radiographic
response.
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2018
Index
2018
171
Association of Adverse Events (AES) with Eciacy Outcomes
for Cabozantinib (C) in Patients (PTS) with Advanced
Hepatocellular Carcinoma (AHCC) in the Phase 3 Celestial Trial
Oliver Waidmann 1; G.K. Abou-Alfa 2; T. Meker 3; A.-L. Cheng 4; I. Cicin 5;
L. Bolondi 6; H.J. Klümpem 7; S.L. Chan 8; V. Dadduzio 9; S. Milwee 10;
S. Dubey 2; R.K. Kelley 11; A.B. El-Khoueiry 12
1Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland
2Memorial Sloan-Kettering Cancer Center, New York, United States
3University College London Hospital, London, United Kingdom
4National Taiwan University Hospital, Taipei, Taiwan
5Trakya University Hospital, Erdime, Turkey
6Universität Bologna, Bologna, Italien
7Amsterdam University Medical Centre, University Amsterdam, Amsterdam,
Niederlande
8State Key Laborotory of oncolocgy, Chinese University of Hong Kong,
Hong Kong
9Institute Oncology Veneto, Padova, Italien
10Exelixis Inc, South San Francisco, United States
11UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco,
United States
12USC Norris Comprehensive Cancer Center, Los Angeles, United States
Purpose: Class-specic AEs occurring with tyrosine kinase inhibitors
have been associated with improved ecacy outcomes in several tu-
mor types including aHCC. In the CELESTIAL trial C improved overall
survival (OS) and progression-free survival (PFS) vs placebo (P) in pts
with previously treated aHCC. Here, we retrospectively evaluate the as-
sociation of palmar-plantar erythrodysaesthesia (PPE) and hypertension
(HTN) with OS and PFS for C in the CELESTIAL trial.
Methods: 707 pts with aHCC were randomized 2:1 to receive 60 mg C
or P once daily. Eligible pts had Child-Puqh score A, ECOG PS ≤1, must
have received prior sorafenib and could have received up to two prior reg-
imens of systemic therapy for HCC. OS and PFS with C were evaluated
for pts with any grade PPE or ≥ grade 3HTN within the rst 8 weeks of
study treatment.
Results: Overall, 374 (80%) pts in the C arm and 179 (76) pts in the P
arm completed ≥ 8 weeks of treatment. In the rst 8 weeks, 188 (40%) of
C-treated pts developed any grade PPE vs 11 (5%) of P-treated pts and 61
(13%) of C-treated pts developed grade ≥3 HTN vs 3 (1%) of P-treated
pts. Median OS with C was 14.4 mo for pts with any grade PPE vs 3.4 mo
for pts without PPE (HR 0.59, 95% CI 0.47-0.74) and median PFS with C
was 6.5 mo vs 3.7 mo, respectively (HR 0.63,95% CI 0.51-0.78). Median
OS with C was 16.1 mo for pts with grade ≥3 HTN vs 9.5 mo for pts
without grade ≥3 HTN (HR 0.56, 95 CI 0.39-0.80), and median PFS with
C was 7.4 mo vs 4.4 mo, respectively (HR 0.59, 95% CI 0.43-0.82). Some
imbalances in baseline (BL) characteristics were present. Pts with PPE had
better ECOG PS (60% vs 47% ECOG 0), better liver function (48% vs 34%
ALBl grade 1), and less macrovascular invasion (24% vs 30%) than those
without. Likewise, pts with grade ≥3 HTN had better ECOG PS (61% vs
51% ECOG 0), better liver function (56% vs 37% ALBI grade 1), and less
macrovascular invasion (20% vs 29%) than those without.
Conclusions: e development of PPE or grade ≥3 HTN with C was as-
sociated with prolonged OS and PFS in pts with previously treated aHCC
although some imbalances in BL characteristics between comparator
qroups were present.
172
Matching-Adjusted Indirect Comparison of Cabozantinib (C)
Versus Regorafenib (R) in Advanced Hepatocellular Carcinoma
(HCC)
Marino Venerito 1; R.K. Kelley 2; P. Mollon 3; J.-F. Blanc 4; B. Daniele 5, 6; T. Yau 7;
A.-L. Cheng 8; V. Valcheva 9; A. Remiro Azocar 10; G. Baio 10; Y. LI 11;
G.K. Abou-Alfa 12
1Universitätsklinikum Magdeburg , Magdeburg, Deutschland
2UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco,
United States
3Ipsen Pharma SAS, Boulogne-Billancourt
4Hospital Haut Leveque, Bordeaux, Frankreich
5G. Rummo Hospital, Benevento, Italien
6Ospedale del Mare, Napoli, Italien
7University of Hong Kong, Hong Kong, Hong Kong
8National Taiwan University Hospital, Taiwan
9IPSEN, Boulogne-Billancourt, Frankreich
10University College London, London, United Kingdom
11IQVIA World Publications Ltd., London, United Kingdom
12Memorial Sloan-Kettering Cancer Center, New York, United States
Purpose: C and R have demonstrated survival benet in second-line
treatment of advanced HCC. e aim of this matching-adjusted indirect
comparison (MAIC) was to compare the safety and ecacy of C and R
for patients with HCC who have received sorafenib (S) as the only prior
systemic therapy.
Methods: Data from two pivotal trials with C (CELESTIAL (CT) or R
(RESORCE (RT)) in patients with HCC were used. Using MAIC, indi-
vidual-level data (ILD) from patients enrolled in CT who had received
S as the sole prior therapy (N=495) were adjusted to match the average
baseline (BL) characteristics of the 573 patients enrolled in RT, for which
ILD are not available. To compare survival outcomes, ILD were simulated
for regorafenib using the published Kaplan-Meier (KM) curves for the RT.
Parametric distributions were tted to the ILD to model progression-free
survival (PFS) and overall survival (OS). Grade 3/4 treatment-emergent
drug-related adverse events (AEs) aecting >5% of patients in any arm of
either CT or RT were compared.
Results: Aer balancing BL characteristics, the weighted KM curves for
patients receiving C or R were associated with a median (95% Condence
Interval) PFS of 5.59 (4.90–7.26) months and 3.19 (2.78–4.14) months,
respectively (p<0.05, log-rank test); median OS were 11.37 (8.90–16.95)
months for C and 10.79 (9.18–12.30) months for R (p>0.05, log-rank test).
Upon tting and extrapolating the selected models, C treatment was as-
sociated with longer median PFS and OS than R. e median PFS esti-
mate was 5.49 (4.92–6.13) months for C vs 3.39 (3.05–3.78) months for R,
median OS was 11.40 (10.01–12.96) months for C vs 10.29 (9.15–11.56)
months for R. R was associated with lower rates of diarrhea.
Conclusions: In patients who received second-line treatment aer S and
were matched for BL characteristics, C was associated with prolonged me-
dian PFS and OS compared with R, whereas R was associated with low-
er rates of diarrhea than C. However, even aer matching, bias may still
occur in MAIC due to imbalance in unobserved factors, and it cannot
replace a head-to-head randomized control trial.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 61
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2018
Index
2018
174
Quality-Adjusted Life Years Accrued with Cabozantinib in
Patients with Advanced Hepatocellular Carcinoma (AHCC)
in the CELESTiAL Trial
Marino Venerito 1; G.K. Abou-Alfa 2; P. Mollon 3; T. Meyer 4; A.-L. Cheng 5;
A.B. El-Khoueiry 6; R.K. Kelley 7; A.D. Baron 8; F. Benzaghou 9; V. Valcheva 3;
S. Hazra 10; M. Mangeshkar 10; N. Freemantle 4
1Universitätsklinikum Magdeburg, Magdeburg, Deutschland
2Memorial Sloan-Kettering Cancer Center, New York, United States
3Ipsen Pharma SAS, Boulogne-Billancourt, Frankreich
4University College London, London, United Kingdom
5Staatliche Universität Taiwan, Taipei, Taiwan
6Norris Comprehensive Cancer Center, Los Angeles, United States
7UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco,
United States
8California Pacic Medical Center, San Francisco, United States
9Ipsen Innovation, Les Ulis, Frankreich
10Exelixis Inc, South San Francisco, United States
Purpose: In patients previously treated for aHCC, cabozantinib (C) led
to longer overall survival and progression-free survival vs placebo (P)
in the randomized, phase 3 CELESTIAL trial (NCT01908426; N=707).
CELESTIAL was stopped early for benet at the second interim analysis.
is post hoc analysis estimated the incremental quality-adjusted life
years (QALYs) accrued in CELESTIAL.
Methods: Health utility was elicited at each study visit using the EQ-
5D-5L quality of life questionnaire. (completed by 82-100% of patients
overall). UK crosswalk taris were applied for health states. Cumulative
QALYs by patient were calculated by linear interpolation; for patients who
were censored (31% of patients; including 9% within 100 days of random-
ization), the last observed utility value was carried forward to study end.
e dierence in restricted mean QALYs was calculated using generalized
linear models, accounting for baseline utility, and with 0.06-0.08 QALYs
considered the minimal important dierence.
Results: At day 50 aer randomization (acute treatment phase), C was
associated with a small reduction in mean total QALYs vs P (dierence
−0.003; 95% CI −0.005 to −0.002; p≤0.001; n=601 [C n=389; P n=212]).
At day 100, there was a numerical benet in mean total QALYs for C
(dierence +0.007; 95% CI −0.001 to 0.015; p=0.103; n=627 [C n=410; P
n=217]), and at day 150 the dierence was +0.032 QALYs (95% CI 0.017
to 0.047; p≤0.001; n=629 [C n=412; P n=217]) in favor of C. Over the en-
tire follow-up, patients randomized to C accrued a mean of +0.092 (95%
CI 0.016 to 0.169; p=0.018; n=700 [C n=465; P n=235]) additional QA-
LYs compared with those receiving P. Using alternative Devlin weights for
health states, the mean accrued QALYs with C was +0.115 vs P (95% CI
0.032 to 0.198; p=0.007).
Conclusions: Cabozantinib was associated with an initial, small reduc-
tion in health utility. However, with continued treatment, health utility
increased and at the end of the study there was a clinically and statistically
signicant benet in mean QALYs in favor of C.
199
Pet-Directed Combined Modality Therapy for
Gastroesophageal Junction Cancer: First Results of the
Prospective Memori Trial
Sylvie Lorenzen 1; Quante Michael 2; Isabell Rauscher 3;
Julia Slotta-Huspenina 4; Karl-Friedrich Becker 4; Wilko Weichert 4;
Markus Feith 5; Julian Holch 6; Helmut Friess 5; Stephanie Combs 7;
Wolfgang Weber 3; Bernhard Haller 8; Martin Angele 9;
Markus Albertsmeier 9; Christiane Blankenstein 10; Stefan Kaspar 11;
Jens Zimmermann 2; Hana Algül 2; Roland Schmid 2; Markus Schwaiger 3;
Jens Siveke 11
1Technical University Munich, Klinikum rechts der Isar, III. Medizinische Klinik
und Poliklinik, Munich, Deutschland
2Technical University Munich, Klinikum rechts der Isar, II. Medizinische Klinik
und Poliklinik, Munich, Deutschland
3Technical University Munich, Klinikum rechts der Isar, Department of Nuclear
Medicine, Munich, Deutschland
4Technical University Munich, Institute of Pathology, Munich, Deutschland
5Technical University Munich, Klinikum rechts der Isar, Surgical Clinic and
Policlinic, Munich, Deutschland
6Ludwig-Maximilians-Universität München, Department of Medicin III,
München, Deutschland
7Technical University Munich, Klinikum rechts der Isar, Department of Radiation
Oncology, Munich, Deutschland
8Technical University Munich, Klinikum rechts der Isar, Institut für Medizinische
Informatik, Statistik und Epidemiologie, Munich, Deutschland
9Ludwig Maximilian University, Department of General, Visceral and
Transplantation Surgery, Munich, Deutschland
10Technical University Munich, Muenchener Studienzentrum, Munich,
Deutschland
11University Hospital Essen, West German Cancer Center, Division of Solid Tumor
Translational Oncology, DKTK partner site Essen, Deutschland
Purpose: We evaluated a PET-guided treatment stratication for
improvement in obtaining negative surgical margins (R0) in resectable
gastroesophageal junction (GEJ) adenocarcinoma. According to
sequential18F-FDG PET, only 40–50% of patients (pts) respond to
neoadjuvant chemotherapy (CTX). Early PET non-responders (P-NR)
aer induction CTX might benet from chemoradiation (CRT).
Methods: 75 pts with resectable GEJ adenocarcinomas were enrolled in
this interventional, prospective, non-randomized multicenter trial. Pts
underwent baseline 18F-FDG PET scan followed by 1 cycle of CTX (e.g.
EOX, XP, mFOLFOX6). PET was repeated at day 14-21 and responders
(P-R), dened as ≥ 35% decrease in SUVmaxfrom baseline, continued
with CTX. P-NR switched to CRT (41.4 Gy/23 fractions with weekly car-
boplatin/paclitaxel). Pts underwent surgery 4-6 weeks post-CTX/CRT.
Primary objective was improvement of R0 resection rates in P-NR above
a proportion of 70% based on results from the MUNICON1/2 trials. Sec-
ondary endpoints include disease-free survival (DFS), overall survival
(OS), and translational endpoints.
Results: 160 pts with resectable GEJ adenocarcinomas were screened
with PET in three German university centers. Overall, 85 pts (53%) could
not be included due to previously undetectable metastases (40/25%), no
or too low FDG uptake of the primary tumor (21/13%), other reasons
(24/15%). 75 eligible pts were enrolled in the study and 69 were evaluable.
Based on PET criteria, 47 (68%) and 22 (32%) were P-R and P-NR, respec-
tively. R0 resection rates were 94% (44/47) for P-R and 91% (20/22) for
P-NR. Pathologic complete remission (pCR; <10% vital tumor cells), was
33% (15/46) in P-R and 55% (12/22) in P-NR. With a median follow-up
time of 19 months (mo), estimated 18 mo DFS was 71%/61% for P-R/
P-NR, respectively. Observed median 18 mo OS was 95% for P-R and 75%
for P-NR.
Conclusions: Alternative CRT for GEJ adenocarcinoma improved R0-
and pCR rates among pts who were P-NR aer induction CTX. PET re-
sponse was prognostic for a prolonged OS and DFS.
Disclosure Statement: No conicts of interest
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts62
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2018
Index
2018
220
Does Inammation or Malignancy have Specic Impact onto
the Early Postoperative Outcome – Comparison of Pylorus-
Preserving Pancreatic Head Resection by Traverso-Longmire
in Chronic Pancreatitis vs. Cancer of the Pancreatic
Head – Initial Results of a Tertiary Center
Nikolas Scholz 1; Max Grabowski 1; Ronny Otto 2; Roland S. Croner 1;
Henry Ptok 2; Frank Meyer 1
1Dept. of General, Abdominal, Vascular and Transplant Surgery, University
Hospital at Magdeburg, Magdeburg, Deutschland
2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg, Deutschland
Purpose: To investigate the impact of various diagnoses (chronic pan-
creatitis [“Pan.“] vs. cancer of the pancreatic head [“Ca“]) & interindiv.
dierences such as age & accompanying diseases onto the early postop.
outcome in comparable interventional invasiveness, surgical trauma &
surgical intervention(Op)-induced SIRS-associated alterations.
Methods: All consecutive pats. who had undergone Op in Pan. & Ca were
registered & various outcome parameters such as postop. morbidity (gen-
eral/specic complication rates) & 30-d-mortality were determined.
Results: From 2003-2015, overall 315 pats. were registered out of whom
only n=295 (sex ratio: m/w=181:114 [1.59:1]; median age: 59 [range: 20-
82] yrs.) could be evaluated - 197 cases with Ca (66.8%) & 98 individu-
als with Pan. (33.2%). In comparison, median age was 68.5 (37-82) vs. 51
(20-72) yrs. in Ca & Pan. (p<0.001), resp.; mean ASA scoring was 2.3 (Ca
[1-4]) & 2.1 (Pan. [1-4]; p=0.084), resp. Median preop. hospital stay was 2
[0-17] d in both diseases whereas median postop. stay was 18 (Ca [2-88])
& 15 (Pan. [6-48]) d, resp. (p=0.029).
Surprisingly, there were similar general & specic complication rates
of 21.3% (Ca) vs. 21.4% (Pan.) & 40.1% (Ca) vs. 43.9% (Pan.) (p=0.274;
p=0.616), resp.; in addition, there was only a marginal dierence of the
30-d-mortality: 3.6% (Ca) vs. 2.0% (Pan.) (p=0.723).
Univariate analysis resulted in ASA class with a signif. impact onto mor-
bidity (p=0.013).
In pats. with postop. morbidity, the No. of intraop. transfused red cell
packs was signif. greater than in subjects with no morbidity (1.156
vs. 0.304; p=0.000). Morbidity itself had a signif. eect onto mortality
(p=0.000).
Multivariate analysis using logistic regression did not show any signif.
associations.
Conclusions: e initially hypothesized disadvantageous impact of a
malignancy compared with chronic inammation can not be conrmed
based on the morbidity & mortality despite signif. older pats. & a longer
postop. hospital stay.
Disclosure Statement: e authors do not have anything to be disclosed.
221
Does Splenectomy Play a Signicant Role in the Surgical
Outcome of Gastric Cancer?
Ingo Gastinger 1; K. Heine 1; Frank Meyer 2; Ronny Otto 1; Stefanie Wol 2;
Roland S. Croner 2
1AN-Institut für Qualitätssicherung in der operativen Medizin, Otto-von-
Guericke-Universität, Magdeburg, Deutschland
2Klinik für Allgemein-, Viszeral-, Gefäüß- und Transplantationschirurgie,
Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland
Purpose: Splenectomy can be associated with an increase of postop.
complications but a worse 5-yr survival.
Methods: From 01/01/2007-12/31/2009, all patients (nin total=2,897; surgi-
cal depts., n=141) with primary gastric Ca/Tu lesion of the esophagogas-
tric junction (AEG-Tu) who underwent surgery were registered.
Results: Overall, 2,545 patients (=group[gr.] 1) underwent Tu resection.
Gr.2/3/4/5: AEG-Tu (n=475)/distal gastric Ca (n=2,070)/intraop. spleen
injury (n=127)/splenectomy (n=94) due to Tu inltration vs. injury.
Splenectomy rate was 11.1% (n=283) with the highest proportion in AEG-
Tu (19.4%; no signif. dierences among the groups regarding age, sex ratio
& ASA).
Surgical procedures: e highest splenectomy rate was found in transhia-
tally ext. gastrectomy (in total, 30.2%; AEG-Tu, 27.3%; distal gastric Ca,
38.6%).
Morbidity in case of splenectomy was higher overall & depending on Tu
site (the same in general postop. complication rate; specic postop. compli-
cation rate, no dierence).
Lethality post-splenectomy: Only in AEG-Tu, it was signif. higher (15.2
vs. 5.0%).
All splenectomized patients showed a shorter long-term survival (p<0.001;
18 vs. 36 months with preservation of the spleen).
e lowest 5-yr-survival rates were observed in splenectomized AEG-Tu
patients (25%) & in those with splenectomy due to Tu inltration (20%).
Logistic regression: Spleen preservation – signif. independent variable
regarding lower postop. morbidity whereas splenectomy was associated
with higher postop. complication rate. Overall, splenectomy did not pro-
vide a signif. impact onto lethality. However, splenectomy as part of resec-
tion in AEG-Tu was associated with a signif. higher lethality. A tendential
impact of splenectomy onto a lower overall survival was only seen in the
group of AEG-Tu.
Conclusions: Splenectomy – negative predictor for a worse early postop.
& long-term oncosurgical outcome; therefore, it can only be justied by
direct Tu inltration or irreparable spleen injury.
Disclosure Statement: ere is nothing to be disclosed.
367
Anal Cancer – Population-Based Data from the Munich
Cancer Registry
Anne Schlesinger-Raab 1; Claudia Hörl 2; Heinrich Schorer 3; Claus Belka 4;
Stephanie Combs 5; Reinhard Ruppert 6; Jens Werner 7; Helmut Friess 8;
Jutta Engel 9
1Tumorregister München am Klinikum der Universität München, Institut für
Medizinische Informationsverarbeitung Biometrie und Epidemiologie, Ludwig-
Maximilians-Universität München, München, Deutschland
2Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum
Schwabing, München, Deutschland
3Gemeinschaftspraxis für Strahlentherapie am Klinikum Harlaching -
Bogenhausen - Neuperlach, München, Deutschland
4Klinik und Poliklinik für Strahlentherapie und Radioonkologie am Klinikum der
Universität München, Ludwig-Maximilians-Universität München, München,
Deutschland
5Klinik und Poliklinik für RadioOnkologie und Strahlentherapie, Klinikum Rechts
der Isar, Technische Universität München, München, Deutschland
6Klinik für Proktologie und Chirurgie, München Klinik Neuperlach, München,
Deutschland
7Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Klinikum der
Universität München, Ludwig-Maximilians-Universität, München, Deutschland
8Klinik und Poliklinik für Chirurgie, Klinikum Rechts der Isar, Technische
Universität München, München, Deutschland
9Tumorregister München, Bayerisches Krebsregister - Regionalzentrum
München (LGL) am Klinikum der Universität München, Institut für Medizinische
Informationsverarbeitung Biometrie und Epidemiologie, Ludwig-Maximilians-
Universität, München, Deutschland
Purpose: Anal cancer is rare and linked to HPV infections similar to cer-
vical and some oropharyngeal cancers. In Germany, the incidence diers
clearly between men and women (1.3/100,000 vs. 2.0/100,000). Objective
was to reveal sex-related dierences.
Methods: e number of anal cancer diagnoses between 1998 and 2016
registered in the catchment area of the Munich Cancer Registry were
analyzed by sex, and prognostic factors. Cumulative incidence of tumor
progression, and secondary tumors in consideration of competing risks as
well as survival analyses by Kaplan-Meier method and multivariate Cox
regression analysis were conducted.
Results: A total of 1 815 malignant anal tumors were recorded. Aer exclu-
sion of in situ cases, mucosal and skin melanomas, lymphomas, sarcomas,
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and neuroendocrine neoplasia the age-adjusted incidence (European
Standard Population) was 1.2/100,000 in men and 2.0/100,000 in women
without changes since 1998. Excluding death certicate only cases, 1 564
invasive anal carcinoma were nally analyzed. Median age at initial diag-
nosis accounted for 65.1 years, men were 2 years younger than women.
Age and male/female ratio of 1:2 did not change over the observed time.
TNM-categories were similar frequent in men and women. Whereas G3
tumors were signicantly more in women (39% vs. 28%) and adenocarci-
nomas were more in men (7.8% vs 3.2%).
Conclusions: Women have a better outcome in anal cancer; although no
tumor-specic characteristics were attributed to this dierence.
404
Induction Chemotherapy in Locally Advanced Pancreatic
Cancer (LAPC) - Final Results of a Multicenter Randomized
Phase 2 AIO Trial (NEOLAP)
Ingo Hartlapp 1; Hana Algül 2; Eray Gökkurt 3; Gabriele Siegler 4;
Uwe Martens 5; Dirk Waldschmidt 6; Uwe Pelzer 7; Elke Hennes 8;
Martin Fuchs 9; Jens Siveke 10; Frank Kullmann 11; Stefan Böck 12;
Thomas J. Ettrich 13; Peter Ferenczy 14; Ralph Keller 15;
Christoph-Thomas Germer 16; Hubert Stein 17; Ingo Klein 16;
Volker Heinemann 18; Volker Kunzmann 1
1Uniklinik Würzburg, Medizinische Klinik II, Internistische Onkologie, Würzburg,
Deutschland
2Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar TU München,
München, Deutschland
3Hematology-Oncology Practice Eppendorf (HOPE), Hamburg, Deutschland
4Paracelsus Medizinischen Universität Nürnberg, Klinik für Innere Medizin 5,
Schwerpunkt Onkologie / Hämatologie, Nürnberg
5SLK-Kliniken Heilbronn GmbH, Klinik für Innere Medizin III: Hämatologie,
Onkologie, Palliativmedizin, Heilbronn, Deutschland
6Uniklinik Köln, Klinik für Gastroenterologie und Hepatologie, Köln, Deutschland
7Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Medizinische Klinik
mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie (CVK),
Berlin
8Überörtliche Gemeinschaftspraxis Schwerpunkt Hämatologie, Onkologie und
Palliativmedizin , MVZ Onkologie Barmbek, Hamburg, Deutschland
9München Klinik Bogenhausen, Klinik für Gastroenterologie, Hepatologie und
Gastroenterologische Onkologie , München
10West German Cancer Center, University Hospital Essen, Essen
11Klinikum Weiden, Medizinische Klinik I, Weiden
12Klinikum der Universität München, Medizinische Klinik und Poliklinik III,
München
13Universitätsklinikum Ulm, Klinik für Innere Medizin I, Ulm
14Clin Assess Gesellschaft für Klinische Forschung GmbH, Leverkusen
15AIO-Studien-gGmbH, Berlin, Deutschland
16Uniklinik Würzburg, Chirurgische Klinik I, Würzburg , Deutschland
17Paracelsus Medizinische Universität Nürnberg, Klinik für Allgemein-, Viszeral-
und Thoraxchirurgie, Nürnberg, Deutschland
18Klinikum der Universität München, Medizinische Klinik und Poliklinik III,
München, Deutschland
Purpose: e best preoperative treatment for LAPC is unknown. NEO-
LAP is the rst prospective, randomized trial to compare nab-Paclitaxel
and Gemcitabine (nPG) with FOLFIRINOX-based induction chemother-
apy in LAPC.
Methods: In this open-label, randomized, two-arm, phase 2 trial, treat-
ment-naive patients (pts) with histologically/cytologically proven non-re-
sectable LAPC were recruited from 33 German centers. Aer two cycles
of nPG induction pts without progressive disease or unacceptable adverse
events (AEs) were randomly allocated (1:1) to receive either two addition-
al cycles of nPG or four cycles of sequential un-modied sqFOLFIRINOX.
Secondary resectability was assessed by surgical exploration in all pts with
at least stable disease (SD) aer completion of induction chemotherapy.
e primary endpoint was conversion rate (R0/R1 resection). Secondary
endpoints included overall survival (OS), safety, CA 19-9 response and
central radiological review.
Results: 168 pts were registered and 130 were randomly allocated (64
to nPG and 66 to sqFOLFIRINOX). Conversion rate was 30.6 vs 45.0%
(Odds ratio 0.54; 95% CI, 0.26 to 1.13; P = 0.135), OS 17.3 vs 22.5 months
(adjusted HR 0.73; 95% CI, 0.42 to 1.28; P = 0.268), AEs ≥ grade 3 54,7 vs
53,0%, (investigator assessed) ORR 22.6 vs 21.7%; DCR 82.3 vs 75.0%, CA
19-9 response (baseline to week 16); -62.2 % vs -56.7 %, major pathologi-
cal response (<10% viable tumor cells) 15 vs 9.5% in the nPG (n=62) and
sqFOLFIRINOX (n=60) arm, respectively. Among all ITT-pts (N=165)
conversion was associated with signicant improved OS (27.4 vs. 14.2
months; P = 0.0035). First results from central radiological review with
regard to primary and secondary resectability status and tumor response
will be presented.
Conclusions: Secondary resection aer 4 months of induction chemo-
therapy followed by surgical exploration is feasible in about 1/3 of pts with
LAPC and associated with markedly prolonged OS without signicant
dierence in safety or ecacy endpoints between nPG and sqFOLFIRI-
NOX arm.
Disclosure: Supported by Celgene + AIO-Studien-gGmbH
433
Immunohistochemical Proling of Liver Metastases and
Matched-Pair Analysis in Patients with Metastatic Pancreatic
Ductal Adenocarcinoma
Thomas Held 1; Caroline S. Verbeke 2; Oliver Strobel 3; Wiktor Rutkowski 4;
Christina Villard 5; Carlos Fernández Moro 6; Marco Del Chiaro 5;
Markus Büchler 3; Matthias Löhr 4
1Department of Radiation Oncology, Heidelberg University Hospital,
Heidelberg, Deutschland
2Institute of Clinical Medicine, University of Oslo, Oslo, Norwegen
3Department of General, Visceral and Transplantation Surgery, Heidelberg
University Hospital, Heidelberg, Deutschland
4Department of Clinical Intervention and Technology (CLINTEC), Karolinska
Institute, Stockholm, Schweden
5Department of Cancer, Karolinska University Hospital, Stockholm, Schweden
6Department of Pathology, Karolinska University Hospital, Stockholm,
Schweden
Purpose: e purpose of the current study was to investigate the immu-
nohistochemical (IHC) prole of liver metastases (LM) from patients with
pancreatic ductal adenocarcinoma (PDAC).
Methods: Liver biopsies from seventy-seven (n = 77) patients with PDAC
diagnosed between 2010 and 2014 were evaluated regarding expression of
15 IHC markers. In a separate subgroup analysis (n = 12), paired samples
(LM and primary tumor) from the same patient were investigated for dis-
cordance in the IHC prole.
Results: LM were classied as pancreatobiliary-type (PB-type) in 72
cases (93.5%), intestinal-type (INT-type) in four cases (5.2%) and squa-
mous in one case (1.3%). ere was no signicant dierence in overall
survival (OS) between LM of PB-type or INT-type (p = 0.097). In multi-
variate analysis, age < 70 years (p = 0.047), absence of SMAD4 mutation
(p = 0.026), absence of CDX2 expression (p = 0.003) and well to mod-
erate dierentiation were signicant prognostic factors for better OS in
patients with LM (p = 0.031). Analysis of paired tissue samples from LM
and primary tumor revealed marked discordance in CDX2 (50% gained,
p = 0.125) and SMAD4 (33% loss of SMAD4, p = 0.375).
Conclusions: CDX2 expression and SMAD4 mutation indicate poor out-
come in patients with LM of PDAC. Matched-pair analysis reveals discor-
dance in expression of distinct IHC markers.
References:
Not applicable.
Disclosure Statement: e authors declare no conicts of interest.
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444
Patient with Severe Symptomatic Aortic Valve Insuciency
and Multiple Small Strokes Due to Nonbacterial Thrombotic
Endocarditis (NBTE) Diagnosed with Metastatic Pancreatic
Cancer
Maike Collienne 1, 2; Martin Kuhns 2, 3; Hans-Peter Hauber 2, 4; Dirk Arnold 1
1Onkologie mit Sektion Hämatologie, Asklepios Klinik Altona, Hamburg,
Deutschland
2Antibiotic Stewardship-Team, Asklepios Klinik Altona, Hamburg, Deutschland
3Fachgebiet Mikrobiologie, Medilys Laborgesellschaft mbH, Hamburg,
Deutschland
4Kardiologie, Pneumologie und internistische Intensivmedizin, Asklepios Klinik
Altona, Hamburg, Deutschland
Purpose: Patients with metastatic cancer diseases tend to have a hyperco-
agulopathy with risk of thrombosis, arterial embolization and, in conse-
quence, ischemic strokes. One of the known causes is NBTE.
Methods/Patient characteristics: A 51-year old athletic man with
metastatic pancreatic adenocarcinoma presented with aphasia and
memory gaps for four days aer initiation of chemotherapy (FOLFIRINOX
regimen).
Results: A cerebral MRI showed a pattern of multiple small ischemic le-
sions. A transesophageal echocardiography revealed a severe aortic valve
insuciency with mobile vegetation. An empiric antibiotic treatment
with ampicillin, ucloxacilline and gentamicin was initiated. e patient
had to undergo biological aortic valve replacement. As a possible source of
infection, the port catheter was removed. Microbiology showed no patho-
logical evidence of infective endocarditis. erefore, the duration of an
antibiotic treatment was limited to 22 days.
Pre-medical history showed that the patient already had previous periph-
eral venous thrombosis one month ago. During the current treatment,
multiple thrombophlebitic events occurred despite anticoagulation. Fur-
ther inspections regarding dierent causes of NBTE showed no patholog-
ical ndings. However, a histopathological examination of the aortic valve
had not been done.
During the management period, CA19-9 levels rose and CT scan showed
disease progression of the pancreatic tumor and the hepatic metastases.
erefore, chemotherapy was re-induced and a new port catheter was im-
planted.
Conclusions: is is a rare but manageable consequence of paraneoplastic
hypercoagulopathy in metastatic pancreatic cancer despite oral
anticoagulation.
Disclosure Statement: e authors have no conict of interest.
452
Analysis of Central versus Local Deviating HER2 Test Results
in Gastric Cancer in the Multicenter Varianz Study
Katharina Kolbe 1; Ivonne Haner 1; Katrin Schierle 2; Dieter Maier 3;
Birgitta Geier 3; Birgit Luber 4; Albrecht Kretzschmar 5;
Ludwig Fischer von Weikersthal 6; Miriam Ahlborn 7; Jorge Riera 8;
Beate Rau 9; Gabriele Siegler 10; Stefan Fuxius 11; Thomas Decker 12;
Christian Wittekind 2; Florian Lordick 1
1UCCL, Universitätsklinikum Leipzig, Leipzig, Deutschland
2Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
3Biomax Informatics AG, Planegg, Deutschland
4Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische
Universität München, München, Deutschland
5Internistische Onkologie und Hämatologie, Klinikum St. Georg Leipzig,
Leipzig, Deutschland
6 Praxis für Hämatologie und Internistische Onkologie, Klinikum St. Marien
Amberg, Amberg, Deutschland
7Hämatologie & Onkologie, Kllinikum Braunschweig, Braunschweig,
Deutschland
8Klinik für Hämatologie, Onkologie und Palliativmedizin, Universitätsklinikum
Marburg, Marburg, Deutschland
9Chirurgische Klinik Campus Charité Mitte / Campus Virchow-Klinikum
CCM/CVK , Charité Berlin, Berlin, Deutschland
10Innere Medizin Onkologie / Hämatologie, Klinikum Nürnberg Nord, Nürnberg,
Deutschland
11Onkologische Schwerpunktpraxis Heidelberg am Römerkreis, Heidelberg,
Deutschland
12Gemeinschaftspraxis für Hämatologie und Onkologie GbR, Wangen im Allgäu,
Deutschland
Purpose: VARIANZ is a non-interventional study funded by BMBF
(01ZX1610E) recruiting patients (pts) receiving treatment for stage IV
gastric cancer. e primary objective of VARIANZ is to investigate resis-
tance factors of HER2 target therapy. Locally assessed HER2 status was
re-assessed centrally using immunohistochemistry (IHC) and in situ hy-
bridization. In 22.2% of all pts HER2 status was not conrmed. Only pts
with conrmed HER2+ status seem to benet from trastuzumab. Here,
we aimed to investigate causes of HER2 discrepancies between local and
central pathologies.
Methods: Information about HER2 test procedures, antibodies for IHC
and participation in round robin tests was collected from participating
pathologies (n=105). Tumor samples with central and local HER2 tests
(n=375) were grouped: central HER2+ concordant to local HER2 status
(HER2+/HER2+) and central HER2- deviating from local HER2 status
(HER2-/HER2+).
Results: Type of antibody used in local pathology and participation in
round robin tests did not inuence HER2 deviation rate. In central
testing, cytoplasmatic HER2 staining of tumor cells was detected in
60.3% of HER2-/HER2+ probes compared to 40.6% in HER2+/HER2+
(p< 0.05, Chi² -test). Concordant to this result the percentage of HER2
membrane stained tumor cells was low in HER2-/HER2+ (13.97 ±
21.87%) vs. HER2+/HER2+ (61.19 ± 31.31%; p< 0.001, Mann-Whitney-
test). 32% of tumor samples originated from surgical resection specimens
in HER2-/HER2+ vs. 9% in HER2+/HER2+ (p< 0.001, Chi² -test). e
majority of pts undergoing surgery received neoadjuvant chemotherapy
(54% of HER2-/HER2+, 66.7% of HER2+/HER2+ pts).
Conclusions: Identication of pts who benet from HER2 targeting ther-
apy remains challenging. e extent of cytoplasmatic HER2 staining and
potential misinterpretation as HER2+ status may inuence test results.
Beyond that, the use of surgical resection specimens for assessment of
HER2 seems to lead to less robust results compared to the use of biopsy
material.
Disclosure Statement: none
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476
Treatment of HER2 Positive Advanced Gastric Cancer:
Deviations in HER2 Results and Its Impact on Survival
Ivonne Haner 1; Katrin Schierle 2; Dieter Maier 3; Birgitta Geier 3;
Elba Raimundez 4, 5; Jan Hasenauer 4, 5; Birgit Luber 6; Albrecht
Kretzschmar 7; Ludwig Fischer von Weikersthal 8; Miriam Ahlborn 9;
Jorge Riera 10; Beate Rau 11; Gabriele Siegler 12; Stefan Fuxius 13;
Thomas Decker 14; Christian Wittekind 2; Florian Lordick 1
1UCCL, Universitätsklinikum Leipzig, Leipzig, Deutschland
2Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
3, Biomax Informatics AG, Planegg, Deutschland
4Hausdor Center for Mathematics - HCM, Universität Bonn, Bonn, Deutschland
5Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg,
Deutschland
6Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische
Universität München, München
7MVZ Mitte, Leipzig, Deutschland
8Praxis für Hämatologie und Internistische Onkologie, Klinikum St. Marien
Amberg, Amberg, Deutschland
9Medizinische Klinik III Hämatologie/Onkologie, Städtisches Klinikum
Braunschweig, Braunschweig , Deutschland
10Klinik für Hämatologie und Onkologie , Universitätsklinikum Marburg ,
Marburg , Deutschland
11Chirurgische Klinik Campus Charité Mitte , Campus Virchow-Klinikum
CCM/CVK, Berlin, Deutschland
12Innere Medizin Onkologie / Hämatologie, Klinikum Nürnberg, Nürnberg,
Deutschland
13Onkologische Schwerpunktpraxis Heidelberg, Heidelberg
14Gemeinschaftspraxis für Hämatologie und Onkologie, Ravensburg,
Deutschland
Purpose: Trastuzumab is the only approved target therapy for HER2 pos-
itive (HER2+) gastric cancer (GC) and used in stage IV 1st line treatment.
Not all treated HER2+ patients respond and most initial responders ex-
perience progression. e resistance mechanisms for trastuzumab in GC
are poorly understood. e aim of the VARIANZ study (NCT02305043,
grant: BMBF 01ZX1610E) was to investigate the biological background of
resistance to HER2 directed target therapy in GC.
Methods: Patients (pts) receiving medical treatment for stage IV GC were
recruited in 34 German sites and followed up to 48 months. HER2 sta-
tus was veried centrally using immunohistochemistry and chromogen-
ic-in-situ hybridization. In addition, HER2 gene expression was assessed
using qPCR.
Results: 548 pts were enrolled and 521 samples were characterized for
HER2. 89 of 521 samples were found HER2+ in central testing. In 78 sam-
ples the locally assessed HER2+ status could not be centrally conrmed.
e deviation rate between local and central testing was 22.2%. In con-
rmed HER2+ GC more tumor cells stained positive for HER2 (61.19
± 31.31% [SD] vs. 13.97 ± 21.87% [SD]; p< 0.001) and a higher HER2/
CEP17 amplication was found (7.31 ± 5.58 [SD] vs. 1.78 ± 0.80 [SD];
p< 0.001). Furthermore, HER2 gene expression (∆Ct) was signicantly
higher in conrmed HER2+ GC (41.83 ± 1.63 [SD] vs. 39.05 ± 1.78 [SD];
p< 0.001).
Pts with a conrmed HER2+ status had a signicantly longer overall sur-
vival when treated with trastuzumab plus chemotherapy (18.6 months
[95%-CI 15.7 - 21.5; n=62] vs. 9.6 months [95%-CI 6.6 – 12.6, n=67], HR
for death 0.45, p< 0.001).
Conclusions: Discrepancies in HER2 assessment in GC between central
pathology and local sites were signicant and mostly found in tumor
specimens with intermediate HER2 levels. Borderline HER2-positivity
and heterogeneity of the marker expression should be considered as a
resistance factor for HER2-directed therapy. HER2-cut-os should be re-
considered and detailed HER2 reports including quantication of stained
tumor cells and HER2 amplication levels might be of value.
535
Somatostatin and Chemokine CXCR4 Receptor Expression
in Pancreatic Adenocarcinoma Relative to Pancreatic
Neuroendocrine Tumours
Ylberta Kajtazi 1; Daniel Kämmerer 2; Jörg Sänger 3; Stefan Schulz 1;
Amelie Lupp 1
1Institute of Pharmacology and Toxicology, Jena University Hospital, Jena,
Deutschland
2Department of General and Visceral Surgery, Zentralklinik Bad Berka,
Bad Berka, Deutschland
3Laboratory of Pathology and Cytology, Zentralklinik Bad Berka, Bad Berka,
Deutschland
Purpose: Pancreatic adenocarcinoma (PAC) represents one of the most
devastating types of cancer with an exceptionally poor prognosis. ere-
fore, improved diagnostic and treatment approaches are urgently need-
ed. An over-expression of somatostatin receptors (SST) as well as of the
chemokine receptor CXCR4 has been shown for many tumor entities. Re-
spective expression data for PAC, however, are scarce and contradictory.
Methods: Overall, 137 tumor samples from 70 patients, 26 of whom
were diagnosed with PAC and 44 with pancreatic neuroendocrine tumor
(PanNET), were compared in terms of SST and CXCR4 expression by im-
munohistochemical analysis using well-characterized rabbit monoclonal
antibodies.
Results: In PAC tumors, only SST1 and CXCR4 expression was detect-
able. SST1 was present in 42.3% and CXCR4 in 7.7% of the cases. e
overall staining intensity, however, was very weak. In contrast to the
tumor cells, in many PAC cases, tumor capillaries showed strong SST3,
SST5 or CXCR4 expression. In PanNETs, SST2 was the most-prominent-
ly expressed receptor. It was observed in 75.0% of the tumors at medi-
um-strong intensity. SST5, SST1 and CXCR4 expression was detected in
20.5%, 15.9% and 11.4% of PanNET cases, respectively, but the staining
intensity for these receptors was only weak. SST2 positivity in PanNET,
but not in PAC, was associated with favorable patient outcomes.
Conclusions: In contrast to PanNET, SST or CXCR4 expression in PAC
is clearly of no therapeutic relevance. However, indirect targeting of these
tumors via SST3, SST5 or CXCR4 on tumor microvessels may represent a
promising additional therapeutic strategy.
Disclosure Statement: Daniel Kaemmerer received funding and support for travel
to meetings from IPSEN and PFIZER. All other authors have nothing to declare.
646
Periampullary Cancer - Survival Among Patients
with Resistant Bacteribilia
Sebastian Homann; Andreas Luu; Orlin Belyaev; Waldemar Uhl
Department of Surgery, St. Josef Hospital Bochum, Ruhr University Bochum,
Bochum, Deutschland
Purpose: In pancreatic surgery preoperative biliary drainage is associated
with bacteribilia, which is more and more frequently caused by resistant
microorganisms. Resistant microorganisms increase the risk for postsur-
gical complications, which may delay recovery and adjuvant therapy. e
question if resistant microorganisms also reduce long term survival is not
answered, yet.
Methods: We performed a prospective survival analysis among all pa-
tients with periampullary cancer who underwent pancreatic head resec-
tion or biliary bypass surgery at St. Josef Hospital, Ruhr University Bo-
chum, from January 2011 until December 2015. e nal date for survival
evaluation was August 31st 2016. Intraoperative bile duct cultures were
collected among all patients immediately aer bile duct transection.
Results: 430 patients were included. e frequency of bacteribilia was 66
%, bacteribilia with resistant microorganisms was 17 %. In 41 % patients
with resistant microorganisms had undergone preoperative antibiotic
therapy, vs. 20 % in patients without resistant microorganisms (p<0.001).
ere were signicantly more postsurgical infectious complications (33 %
vs. 17 %; p=0.003), wound infections (10 % vs. 3 %; p=0.019) and sepsis
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2018
(7 % vs. 2 %; p=0.049) among patients with resistant microorganisms. e
overall survival was 35 % for patients with resistant microorganisms, vs.
51 % for patients without resistant microorganisms (p=0.024). Aer pal-
liative bypass surgery the 3 year survival rate was 25 % for patients with
resistant microorganisms, vs. 34 % for patients without resistant micro-
organisms (p=0.540). Aer R0 resection the 3 year survival rate was 33%
for patients with resistant microorganisms, vs. 62 % for patients without
resistant microorganisms (p=0.055).
Conclusions: Bacteribilia with resistant microorganisms is associated
with higher risk for postsurgical complications with reduced long term
survival. Strategies to avoid bacteribilia with resistant microorganisms
include avoidance of preoperative biliary drainage and rational use of
antibiotics.
759
Histone Deacetylases Expression and Activity in Esophageal
Adenocarcinoma Cells in Vitro
René Thieme 1; Robert Nowotny 1; Ronja Maly 1; Orestis Lyros 1;
Finn K. Hansen 2; Ines Gockel 1
1Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-,
Transplantations-, Thorax- und Gefäßchirurgie
2Universität Leipzig, Pharmazeutische/Medizinische Chemie, Institut für
Pharmazie
Purpose: e response of EAC patients to common chemotherapeutic
regimens is relatively low (approx. 50%). Improving the response rate in
cancer patients is challenging and novel therapeutic treatment options are
needed. Histone deacetylases (HDAC), an enzyme class with promising
novel features, are involved the regulation of gene expression aecting the
epigenom.
Methods: e expression of Zn2+-dependent HDACs and the endoge-
nous HDAC activity were characterized in a Berretts esophagus in vitro
model, containing cells from squamous epithelium, Barrett’s metaplasia,
dysplasia and EAC. Proliferation assays were carried out in EAC cells to
determine cell response to an experimental, HDAC1-3 specic, HDAC
inhibitor (HDACi) in comparison to vorinostat (pan HDACi). e HDAC
activity, the p21 expression, and the histone H3 acetylation were investi-
gated under HDACi treatment.
Results: All Zn2+-dependent HDACs were expressed by each stage of the
Berrett’s esophagus in vitro model. However, the expression intensity was
variable. Vorinostat showed an inhibition of proliferation in the EAC
cells OE33 and OE19 (IC50 of 1.1µM and 1.8µM), while the experimen-
tal HDACi DDK137 revealed an increased anti proliferative eect (IC50
of 0.4µM and 0.6µM), a higher HDAC activity reduction, and higher in-
crease in H3 acetylation. e p21 mRNA-expression showed a cell line,
time and inhibitor specic increase. e highest increase was determined
in OE33 cells (2.5fold) by DDK137 aer 48h, while no increase in p21 was
measured under vorinostat treatment.
Conclusions: We could show a pharmacological more potent HDACi
than vorinostat in EAC cells in vitro. However, further studies are neces-
sary to evaluate the signicance of HDACi and whether HDACi are able
to increase chemosensitivity in EAC patients.
Disclosure Statement: None.
761
Intratumoral Bacterial Lipopolysaccharide (LPS) Detection
as Negative Predictor of Gemcitabine Ecacy in Advanced
Pancreatic Cancer: Translational Results from the AIO-PK0104
Phase 3 Study
Stefan Böck 1, 2; Michael Guenther 3; Volker Heinemann 1, 2; Stephan Kruger 1;
C. Benedikt Westphalen 1; Michael von Bergwelt-Baildon 1, 2;
Thomas Kirchner 2, 3; Michael Haas 1; Steen Ormanns 3
1Department of Internal Medicine III and Comprehensive Cancer Center,
Ludwig-Maximilians-University of Munich, München, Deutschland
2German Cancer Consortium (DKTK), partner site München, Deutschland
3Institute of Pathology, Ludwig-Maximilians-University of Munich, München,
Deutschland
Purpose: A recent pre-clinical study provided evidence that intratumoral
bacteria may mediate gemcitabine resistance by the expression of a long
isoform of the bacterial enzyme cytidine deaminase. is study was con-
ducted in order to determine whether intratumoral LPS detection by IHC
(as surrogate for gram-negative bacterial colonization) is associated with
outcome in advanced pancreatic ductal adenocarcinoma (PDAC) treated
with gemcitabine and non-gemcitabine containing 1st-line chemotherapy.
Methods: Retrospective analysis of archival tumor tissue from 130 pa-
tients treated within the randomized, crossover phase 3 trial AIO-PK0104
(NCT00440167); validation in a second patient cohort (n=113) from a
prospective biomarker study. e correlation of intratumoral LPS to pro-
gression free survival (PFS) and overall survival (OS) was calculated using
the Kaplan-Meier method. Hazard ratios were estimated by Cox propor-
tional hazards regression.
Results: In 31 out of 130 patient samples (24%) from the AIO-PK0104
study intratumoral LPS was detected; in patients with LPS positive tumors
median OS was estimated with 4.4 months, compared to 7.3 months in
patients with LPS negative tumors (HR 1.732, p=0.010). is dierence
in OS was also detected in the subgroup of patients treated with 1st-line
gemcitabine-based treatment (n=71; HR 2.377, p=0.002), whereas no
dierence in OS was observed in the non-gemcitabine subgroup (n=59;
HR 1.275, p=0.478). Within the validation cohort, the LPS positivity rate
was 23% (26 out of 113 patient samples) and LPS detection equally cor-
related with impaired OS in the gemcitabine-based treatment subgroup
(n= 94; HR 1.993, p=0.008) whereas no dierence in OS was observed in
the smaller non-gemcitabine-based treatment subgroup (n=19; HR 2.596,
p=0.219).
Conclusions: e detection of intratumoral bacteria by LPS immunohis-
tochemistry may serve as a negative predictor for gemcitabine ecacy;
this nding indicates a potential role of antibiotic pre-/co-treatment to
overcome bacteria-mediated chemotherapy resistance.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 67
Inhalt
2018
Index
2018
788
Nivolumab versus Chemotherapy in Advanced Esophageal
Squamous Cell Carcinoma (ESCC): The Phase 3 attraction-3
Study
Peter Thuss-Patience 1; Byoung Chul Cho 2; Ken Kato 3;
Masanobu Takahashi 4; Morihito Okada 5; Chen-Yuan Lin 6; Keisho Chin 7;
Shigenori Kadowaki 8; Myung-Ju Ahn 9; Yasuo Hamamoto 10;
Yuichiro Doki 11; Chueh-Chuan Yen 12; Yutaro Kubota 13; Sung-Bae Kim 14;
Chih-Hung Hsu 15; Eva Holtved 16; Ioannis Xynos 17; Mamoru Kodani 18;
Yuko Kitagawa 19
1Med. Klinik m.S. Hämatologie, Onkologie u. Tumorimmunologie,
Charité – Universitätsmedizin Berlin, Berlin, Deutschland
2Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Südkorea
3National Cancer Center Hospital Tokyo, Tokio, Japan
4Tohoku University Hospital, Sendai, Japan
5Hiroshima University Hospital, Hiroshima, Japan
6China Medical University Hospital and School of Pharmacy, China Medical
University, Taichung City, Taiwan
7Cancer Institute Hospital Tokyo, Tokio, Japan
8Aichi Cancer Center Hospital, Nagoya, Japan
9Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Südkorea
10Keio Cancer Center, School of Medicine, Keio University, Tokio, Japan
11Osaka University Hospital, Osaka, Japan
12Taipei Veterans General Hospital, Taipei, Taiwan
13Showa University Hospital, Tokio, Japan
14Asan Medical Center, University of Ulsan College of Medicine, Seoul, Südkorea
15National Taiwan University Hospital, Taipei City, Taiwan
16Odense University Hospital, Odense, Dänemark
17Bristol-Myers Squibb, Uxbridge, United Kingdom
18ONO Pharmaceutical Company Ltd., Osaka, Japan
19Keio University School of Medicine, Tokio, Japan
Purpose: We report the nal analysis from the phase 3 ATTRACTION-3
study of the programmed death (PD)-1 inhibitor nivolumab (NIVO)
vs chemotherapy (CT) in patients (pts) with unresectable advanced or
recurrent ESCC refractory or intolerant to 1 prior uoropyrimidine/
platinum-based CT.
Methods: Pts were enrolled regardless of tumor PD-ligand 1 (PD-L1)
expression and randomized 1:1 to either NIVO (240 mg Q2W) or inves-
tigator’s choice of paclitaxel or docetaxel. Primary endpoint was overall
survival (OS).
Results: 419 pts were randomized (NIVO = 210, CT = 209). At a mini-
mum follow-up of 17.6 months (mo), NIVO showed a statistically signif-
icant improvement in OS vs CT (HR for death 0.77 [95% CI 0.62–0.96;
P = 0.02]; median OS [95% CI], 10.9 mo [9.2–13.3] vs 8.4 mo [7.2–9.9]).
e proportion of pts alive at 18 mo was numerically larger with NIVO
(31%) vs CT (21%). HRs for the risk of death favored NIVO over CT
across tumor PD-L1 expression levels (PD-L1 ≥ 1%, HR 0.69 [95% CI
0.51–0.94]; PD-L1 < 1%, HR 0.84 [95% CI 0.62–1.14]). Objective response
rates (95% CI) were 19% (14–26) with NIVO and 22% (15–29) with CT.
Responses (median [95% CI]) were more durable with NIVO (6.9 mo
[5.4–11.1] vs CT (3.9 mo [2.8–4.2]). Median (95% CI) progression-free
survival was 1.7 mo (1.5–2.7) with NIVO and 3.4 mo (3.0–4.2) with CT;
12-mo rates were 12% and 7%, respectively. Fewer treatment-related ad-
verse events (TRAEs) were reported with NIVO (any grade, 66%; grade
3–4, 18%) vs CT (any grade, 95%; grade 3–4, 63%). NIVO showed signif-
icant overall improvement in quality of life vs CT through on-treatment
week 42 in the EQ-5D visual analog scale (least square mean, 6.9; 95% CI
3.0–10.9; P < 0.001).
Conclusions: NIVO demonstrated superior OS and a favorable safety
prole vs CT in pts with previously treated advanced ESCC, with survival
benet observed regardless of tumor PD-L1 expression. NIVO may rep-
resent a new standard second-line treatment option for pts with advanced
ESCC.
Disclosure Statement: PT-P has been on ad boards and received personal
fees from Lilly, Roche, MSD, BMS, Pzer, and Merck. KK reports serving as a
consultant for ONO Pharmaceutical, Oncolys BioPharma, BeiGene, and MSD
Oncology; and receiving research funding from ONO Pharmaceutical, BeiGene,
MSD Oncology, and Shionogi, outside the submitted work. B-CC reports receiving
honoraria from ONO Pharmaceutical, during the conduct of this study; and stock
ownership of eraCanVac, Inc.; holding patents for Champions Oncology; serv-
ing as a consultant for ONO Pharmaceutical and Bristol-Myers Squibb; receiving
research funding from Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST,
Champions Oncology, Janssen, Yuhan, ONO Pharmaceutical, Dizal Pharma, and
MSD; receiving honoraria from AstraZeneca, Novartis, Bayer, Mogam Institute,
Champions Oncology, Janssen, Yuhan, Dizal Pharma, and MSD; and serving as
a consultant for AstraZeneca, Novartis, Janssen, Yuhan, MSD, Boehringer-Ingel-
heim, Roche, Pzer, Eli Lilly, and Takeda, outside the submitted work. MT reports
receiving research funding from ONO Pharmaceutical, during the conduct of this
study; and serving as a speaker for ONO Pharmaceutical, Bristol-Myers Squibb,
Daiichi Sankyo, and Taiho Pharmaceutical, outside the submitted work. MO
reports serving as speaker for Taiho Pharmaceutical, Chugai Pharma, Covidi-
en, Johnson & Johnson, and Lilly; and receiving research funding from Taiho
Pharmaceutical, Nippon Kayaku, Chugai Pharma, Covidien, Johnson & Johnson,
Daiichi Sankyo, Yakult Honsha, Lilly Japan, Nihon Medi-Physics, Pzer, Mochida
Pharmaceutical Co., Ltd., and Shionogi, outside the submitted work. SK reports
receiving research funding from ONO Pharmaceutical and Bristol Myers-Squibb
during the conduct of this study; and receiving research funding from Lilly Japan,
Taiho Pharmaceutical, and Boehringer Ingelheim; and receiving personal fees
from Chugai Pharma, Merck Serono, Bayer, Eisai, and Yakult Honsha, outside the
submitted work. M-JA reports receiving honoraria from AstraZeneca, Lilly, MSD,
and Takeda; serving as a consultant for Alpha Pharmaceuticals; and serving as an
advisor with AstraZeneca, Roche, Lilly, MSD, and Takeda, outside the submitted
work. YH reports receiving grants from ONO Pharmaceutical and Bristol-My-
ers-Squibb, during the conduct of this study. YD reports receiving personal fees
from ONO Pharmaceutical, during the conduct of this study; and receiving grants
from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, MSD, Daiichi San-
kyo, Yakult Honsha, Takeda Pharmaceutical, Kaken Pharmaceutical, Abbott Japan,
Eisai, Shionogi, Otsuka Pharmaceutical, Ajinomoto Pharmaceutical, Astellas
Pharma, Tsumura, AstraZeneca, Johnson & Johnson, Nippon Kayaku, Novartis
Pharma, Pzer Japan, CSL Behring, and Nestle; receiving personal fees from Taiho
Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, MSD, Daiichi Sankyo, Yakult
Honsha, Takeda Pharmaceutical, Kaken Pharmaceutical, Abbott Japan, Eisai,
Shionogi, Otsuka Pharmaceutical, Ajinomoto Pharmaceutical, Teijin Pharma,
Sano, Astellas Pharma, Tsumura, AstraZeneca, Asahi Kasei Pharma, Medtronic,
Johnson & Johnson, Olympus, and Intuitive Surgical; and receiving conference
fees from the Japanese Gastric Cancer Association, the Japan Esophageal Society,
and the Japan Surgical Society, outside the submitted work. C-CY reports receiving
research funding from ONO Pharmaceutical, during the conduct of this study; and
receiving honoraria from Lilly, Merck Sharp & Dohme, Amgen, and Eisai; receiv-
ing research funding from Eisai, Eective Pharmaceuticals, and Deciphera Phar-
maceuticals; and holding consulting roles with Lilly and Merck Sharp & Dohme,
outside the submitted work. S-BK reports receiving researching funding from
Novartis, Genzyme, and Dongkook Pharma, outside the submitted work. C-HH
reports receiving honoraria from ONO Pharmaceutical and Bristol Myers-Squibb,
during the conduct of this study; and serving as a consultant for ONO Pharma-
ceutical; receiving research funding from ONO Pharmaceutical; serving in a con-
sulting role for Novartis, Lilly, and MSD; receiving honoraria from Merck Sharp
& Dohme; and receiving research funding for MSD, AstraZeneca, and Genentech,
outside the submitted work. IX reports employment with Bristol-Myers Squibb
and ownership of stock in Bristol Myers-Squibb, outside the submitted work. MK
reports employment with ONO Pharmaceutical and ownership of stock in ONO
Pharmaceutical, outside the submitted work. YK reports receiving honoraria from
ONO Pharmaceutical, during the conduct of this study; and receiving honoraria
from Ethicon, Olympus, Taiho Pharmaceutical, Chugai Pharma, Nippon Kayaku,
and Asahi Kasei; and receiving research funding from Astellas Pharma, Otsuka,
Kyowa Hakko Kirin, Kowa, CSL Behring, Kaken Pharmaceutical, Shionogi, Daiichi
Sankyo, Taiho Pharmaceutical, Takeda, Chugai Pharma, Tsumura & Co., Teijin
Pharma, Medtronic, Boehringer Ingelheim, Merck Serono, Novartis, Asahi Kasei,
Kureha, Sano, Sumitomo Dainippon Pharma, Taisho Toyama Pharma, Nippon
Kayaku, Lilly, Pzer Yakult Honsha, GlaxoSmithKline, Medicon, EA Pharma, Ot-
suka, ONO Pharmaceutical, KCI Licensing, Inc., Nihon Pharmaceutical Co., Ltd.,
Mitsubishi Tanabe Pharma Corporation, Eisai Co., Ltd., Bayer Yakuhin, Ltd, Abbot
Japan Co., Ltd., and FUJIFILM Toyama Chemical Co., Ltd., outside the submitted
work. All other authors report no competing interests.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts68
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2018
Index
2018
800
TGFΒ1 and TGFΒ2 Mediated Epithelial-Mesenchymal
Transition in Esophageal Adenocarcinoma Cells
René Thieme; Olga Chemnitzer; Katharina Götzel; Matthias Mehdorn;
Orestis Lyros; Ines Gockel
Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-,
Thorax- und Gefäßchirurgie
Purpose: e esophageal adenocarcinoma (EAC) is characterized by an
early lymphogenic dissemination and a poor prognosis. e tumor biol-
ogy and the impact of autocrine, paracrine and endocrine mediators are
involved in these mechanisms. For dissemination, the tumor cells need to
escape the solid tumor and invade into new target structures. is mech-
anism is described as epitheliale-mesenchymal transition (EMT), which
could be initiated by TGF-beta.
Methods: Two proliferation and motility of the esophageal adenocarcino-
ma cell lines (OE33, OE19) were analyzed aer TGF-beta1 and TGF-beta2
treatment. EMT marker gene expressions (e.g. vimentin) were assessed by
qRT-PCR.
Results: TGF-beta2 led to a deceased proliferation rate compared to un-
treated and TGF-beta1 treated cells in OE33 cells. In OE19 cells both,
TGF-beta1 and TGF-beta2 treatment resulted in an increased prolifera-
tion compared to untreated cells. In OE33 cells the motility was aect-
ed by TGF-beta1 only, while in OE19 cells the motility was increased
by TGF-beta1 and TGF-beta2 compared to untreated cells. e vimen-
tin mRNA-expression in OE33 cells was increased by TGF-beta1 and
TGF-beta2 (14.7-fold and 25.9-fold). However TGF-beta1 and TGF-beta2
only led to a moderate increase in the vimentin mRNA-expression (4.0-
fold and 1.8-fold) in OE19 cells.
Conclusions: TGF-beta1 and TGF-beta2 induce EMT and cellular mo-
tility in a cell line specic pattern. e responsible intracellular signaling
cascades addressed by TGF-beta1 and TGF-beta2 and their contribution
for dissemination in EAC patients need to be investigated with full details.
Disclosure Statement: None.
822
POLO: Ecacy and Health-Related Quality of Life (HRQOL)
with Maintenance Olaparib Following First-Line Platinum-
Based Chemotherapy (PBC) in Patients (PTS) with a Germline
BRCA Mutation and Metastatic Pancreatic Cancer (MPC)
Anke C. Reinacher-Schick 1; Hedy L. Kindler 2; Pascal Hammel 3;
Michele Reni 4; Eric Van Cutsem 5; Teresa Macarulla Mercade 6;
Michael J. Hall 7; Joon Oh Park 8; Daniel Hochhauser 9; Do-Youn Oh 10;
Giampaolo Tortora 11; Hana Algül 12; Eileen M. O‘reilly 13;
David Mcguinness 14; Karen Cui 15; Katia Schlienger 16; Gershon Y Locker 15;
Talia Golan 17; Dirk Arnold 18
1St. Josef-Hospital, Ruhr University Bochum, Bochum, Deutschland
2The University of Chicago, Chicago, United States
3Hôpital Beaujon (AP-HP), Clichy, and University Paris VII, Paris, Frankreich
4IRCCS Ospedale, San Raaele Scientic Institute, MIlan, Italien
5University Hospitals Gasthuisberg, Leuven and KU Leuven, Leuven, Belgien
6Vall d‘Hebron Institute of Oncology, Vall d‘Hebron University Hospital,
Barcelona, Spanien
7Fox Chase Cancer Center, Philadelphia, United States
8Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Südkorea
9University College London Cancer Institute, London, United Kingdom
10Seoul National University Hospital, Seoul, Südkorea
11Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italien
12Dept. of Internal Medicine II, Klinikum rechts der Isar, Technische Universität
München, München, Deutschland
13Memorial Sloan Kettering Cancer Center, New York, United States
14AstraZeneca, Cambridge, United Kingdom
15AstraZeneca, Gaithersburg, United States
16Merck & Co, Kenilworth, United States
17The Oncology Institute, Sheba Medical Center at Tel-Hashomer, Tel Aviv, Israel
18Asklepios Tumorzentrum Hamburg AK Altona, Hamburg, Deutschland
Purpose: Pancreatic cancer (PC) pts with germline BRCA1 and/or
BRCA2 mutation (gBRCAm) have shown response to PARP inhibitor
olaparib (O) (Kaufmann et al. JCO 2015). HRQoL assessment was a pre-
dened sec. objective.
Methods: POLO is an international, randomized, double-blind, placebo
(P)-controlled trial of pts with gBRCAm and PC who had received ≥16
wks of 1L PBC for metastatic disease without progression. Pts were then
randomized 3:2 to maintenance O tablets (300 mg bid) or P. Treatment
continued until investigator-assessed disease progression or unacceptable
toxicity. Primary endpoint was progression-free survival (PFS) by blind-
ed independent central review (modied RECIST 1.1). HRQoL was sec.
endpoint, assessed using EORTC QLQ-C30 questionnaire at baseline and
every 4 wks until disease progression, discontinuation and 30 days aer
last dose. Scores ranged from 0 to 100; ≥10-point change or dierence
between arms was considered clinically meaningful.
Results: We screened 3315 pts, identied 247 with gBRCAm, randomized
154 (O 92, P 62), and treated 151 (O 90, P 61). Pt characteristics (O/P):
age, median (range) 57 (37–84)/57 (36–75); male, 58%/50%; ECOG per-
formance status 0, 71%/61%. With 104 events, PFS was signicantly im-
proved with O vs P (hazard ratio [HR] 0.53; 95% CI 0.35, 0.82; P=0.0038;
median PFS 7.4 vs 3.8 mo, respectively). At interim overall survival anal-
ysis (46% maturity), HR was 0.91 (95% CI 0.56, 1.46; P=0.68). Grade ≥3
adverse events occurred in 40% of O- and 23% of P-treated pts. HRQoL
was preserved with O, no di. between arms. Additional HRQoL data will
be presented.
Conclusions: Maintenance O provided a statistically signicant and clin-
ically meaningful improvement in PFS in mPC pts with gBRCAm whose
disease had not progressed on PBC. Safety was consistent with the known
prole for O. POLO is the rst Phase III trial to validate a biomarker-driv-
en treatment in PC.
Disclosure Statement: Study was funded by AstraZeneca and is part of an alliance
between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck &
Co., Inc., Kenilworth, NJ, Usa (MSD).
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 69
Inhalt
2018
Index
2018
854
Long-Term Survival Following Pancreaticoduodenectomy for
Pancreatic Ductal Adenocarcinoma of the Pancreatic Head
Andreas Luu; Chris Braumann; Torsten Herzog; Gregor Brentano;
Waldemar Uhl
Department of Surgery, St. Josef Hospital Bochum, Bochum, Deutschland
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease
most commonly diagnosed at an advanced stage presenting with distant
metastases or being irresectable. erefore, 5-year overall survival is ex-
tremely poor being estimated at 2.5%. Less than 20% of patients present
with a resectable tumor. Pancreaticoduodenectomy (PD) is the treatment
of choice in cases of PDAC located in the pancreatic head.
Methods: All patients suering from PDAC of the pancreatic head who
underwent a PD in the period from 2007 – 2014 underwent a chart re-
view. Follow-up investigations were performed at least 5 years to detect
long-term survival (LTS). Univariate and multivariate analyses were per-
formed to identify factors inuencing LTS.
Results: Of 152 patients in the study period, 33 patients (22%) were iden-
tied as long-term surviving patients, surviving at least 5 years aer PD.
Median age was 65 (42-80). Male to female ratio was 22 (66.7%) / 11
(33.3%).
Median carbohydrate antigen (CA) 19-9 level was 87 U/ml (2 - 1136 U/
ml) in the LTS-group being signicantly lower than in the remaining co-
hort (131 U/ml; 1 – 9897 U/ml; p = 0.012).
Univariate analyses of pathohistological features between the LTS – group
and the non - LTS-group showed signicant dierences in lymph node
invasion (16x [48.5%] vs. 94x [61.9%); p = 0.014), lymph node ratio (p =
0.029), perineural invasion (24 [72.7%] vs. 129 [84.9%] and tumor grade
(p < 0.001).
Multivariate analysis identied CA 19 – 9 levels, lymph node metastasis
and tumor grade as independent factors contributing to LTS.
Conclusions:
Pathohistological features such as low lymph node ratio, minimal to no
perineural invasion or low tumor grade as well as low levels of CA – 19 - 9
have a signicant impact on long-term survival aer PD in PDAC.
Disclosure Statement: e authors declare no conict of interests.
Genito-urinary Cancer, including Prostate Cancer
Best-of-Abstracts-Vorträge
64
Health-Related Quality of Life in Long-Term Prostate Cancer
Survivors After Nerve-Sparing and Non-Nerve-Sparing
Radical Prostatectomy – Results from The Multiregional
Procas Study
Salome Adam 1; Eva Martin-Diener 2; Bertrand Camey 3;
Celine Egger Hayoz 3; Isabelle Konzelmann 4; Seyed Mohsen Mousavi 5, 6;
Christian Herrmann 5, 6; Sabine Rohrmann 2, 7; Miriam Wanner 7;
Katharina Staehelin 8; Räto Strebel 9; Marco Randazzo 10; Hubert John 10;
Hans-Peter Schmid 11; Volker Arndt 1, 12
1National Institute for Cancer Epidemiology and Registration (NICER), Zürich,
Schweiz
2Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and
Prevention Institute, Zürich, Schweiz
3Fribourg Cancer Registry, Fribourg, Schweiz
4Health Observatory Valais, Valais Cancer Registry, Sion, Schweiz
5Cancer Registry East Switzerland, St. Gallen, Schweiz
6Cancer Registry Graubünden and Glarus, Chur, Schweiz
7Cancer Registry Zurich and Zug, Zurich, Schweiz
8Basel Cancer Registry, Basel, Schweiz
9Department of Urology, Graubünden Cantonal Hospital, Chur, Schweiz
10Department of Urology, Winterthur Cantonal Hospital, Winterthur, Schweiz
11Department of Urology, St. Gallen Cantonal Hospital, St. Gallen, Schweiz
12Unit of Cancer Survivorship, German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
Purpose: Nerve-sparing (NS) surgery was developed to improve postop-
erative sexual and potentially urological outcomes aer radical prostatec-
tomy (RP). However, it is largely unknown how NSRP aects health-re-
lated quality of life (HRQoL) including urinary and sexual outcomes in
prostate cancer (PC) survivors 5-10 years aer diagnosis in comparison
to Non-NSRP.
Methods: e study population included 382 stage pT2-T3N0M0 PC sur-
vivors 5-10 years post-diagnosis, who were identied from the multire-
gional Prostate Cancer Survivorship in Switzerland (PROCAS) study. Brief-
ly, in 2017/2018, PC survivors were identied via six population-based
cancer registries based in both German- and French-speaking Switzer-
land. HRQoL and PC-specic symptom burden was assessed using the
EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Dierences in
HRQoL outcomes between survivors treated with NSRP (uni- & bilateral)
and Non-NSRP were analysed with multivariable linear regression adjust-
ed for age, years since diagnosis, cancer stage, comorbidities at diagnosis
and further therapies, if appropriate. Multiple imputation was performed
to minimize the bias due to missing data.
Results: 5-10 years aer diagnosis, PC survivors treated with NSRP and
Non-NSRP reported similar symptom burden and comparable HRQoL
function scores. e only signicant dierences were reported for sexual
activity, whereas PC survivors who underwent NSRP reported statistical-
ly signicant (p=0.031) higher sexual activity than those on Non-NSRP.
NSRP and Non-NSRP reported similar scores for urinary symptoms and
all other HRQoL outcomes.
Conclusions: NSRP and Non-NSRP were generally associated with com-
parable long-term HRQoL outcomes, but NSRP was linked with signi-
cantly higher sexual activity scores than Non-NSRP. Our results support
nerve-sparing techniques as an option to improve post-operative sexual
but not urinary outcomes aer RP in long-term PC survivors.
Disclosure Statement: e authors have nothing to disclose.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts70
Inhalt
2018
Index
2018
383
Immune Cell Gene Expression Signature is Associated with
Improved Outcome in Muscle-Invasive Urothelial Bladder
Cancer Patients Treated with Radical Cystectomy
Markus Eckstein 2; Pamela Strissel 3; Reiner Strick 3; Veronika Weyerer 2;
Ralph M. Wirtz 4; Carolin Pfannstiel 2; Adrian Wullweber 2; Fabienne Lange 2;
Philipp Erben 5; Robert Stöhr 2; Simone Bertz 2; Carol I. Geppert 2;
Nicole Furich 2; Helge Taubert 1; Sven Wach 1; Johannes Breyer 6;
Wolfgang Otto 6; Maximilian Burger 6; Christian Bolenz 7; Bastian Keck 1;
Bernd Wullich 1; Arndt Hartmann 2; Danijel Sikic 1
1Department of Urology and Pediatric Urology, University Hospital Erlangen,
Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
2Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-
Universität Erlangen-Nürnberg, Erlangen, Germany
3Department of Gynecology and Obstetrics, University Hospital Erlangen,
Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
4STRATIFYER Molecular Pathology GmbH, Cologne, Germany
5Department of Urology, Medical Faculty Mannheim, Heidelberg University,
Mannheim, Germany
6Department of Urology, University of Regensburg, Regensburg, Germany
7Department of Urology and Pediatric Urology, University Hospital Ulm,
University of Ulm, Ulm, Germany
Purpose: Recently, distinct immune phenotypes in muscle-invasive blad-
der cancer (MIBC) correlating with improved outcome were dened. is
study was conducted to develop a diagnostic assay to assess the immune
status of MIBC and to predict patient outcome aer curative treatment.
Methods: Gene expression of CD3Z, CD8A and CXCL9, dierent im-
mune cell (IC) populations including stromal tumor inltrating lympho-
cytes (sTILs), T-cells, NK-cells, macrophages and PD-1+ IC, and intrinsic
subtypes (MDACC-approach) were assessed in a cohort of 187 curatively
treated MIBC patients (CCC-EMN-cohort). A gene expression signa-
ture was derived by hierarchical-clustering and further validated in the
TCGA-cohort. IC populations in the TCGA cohort were assessed via
CIBERSORT. Benet of platinum-containing adjuvant chemotherapy was
assessed in a pooled cohort of 125 patients.
Results: e gene expression signature of CXCL9, CD3Z and CD8A cor-
relates with quantitative amounts of specic IC populations and sTILs
(CCC-EMN: ρ-range: 0.44-0.74; TCGA: ρ-range: 0.56-0.82) and allows
stratication of three dierent inammation levels in both cohorts (In-
amed high, Inamed low, Uninamed). Highly inamed tumors are
preferentially of basal dierentiation and show favorable 5-year survival
rates of 67.3% (HR=0.27; CCC-EMN) and 55% (HR=0.41; TCGA). Un-
inamed tumors are predominantly of luminal dierentiation and low
5-year survival rates of 28% (CCC-EMN) and 36% (TCGA). Inamed
tumors exhibit higher levels of targetable immune checkpoints PD-1 and
PD-L1. Patients undergoing adjuvant platinum-based chemotherapy with
“inamed high” tumors showed a favorable 5-year survival rate of 64%
(HR=0.27; merged CCC-EMN and TCGA cohort).
Conclusions: e gene expression signature of CD3Z, CD8A and CXCL9
is reliable to assess the immune status of MIBC and to stratify the sur-
vival of MIBC patients undergoing curative treatment and adjuvant plat-
inum-based chemotherapy. It identies tumors with high expression of
immune checkpoints which are targetable by immunotherapy.
763
The Pure High-Grade Papillary Urothelial Carcinoma of the
Urinary Bladder: A Luminal Lesion Characterized by Frequent
Alterations in Genes Encoding Chromatin-Modifying Proteins
Tician Schnitzler 1; Nadina Ortiz-Brüchle 1; Ursula Schneider 1;
Isabella Lurje 1; Karolina Guricova 1; Alexander Buchner 2; Nadine T. Gaisa 1;
Ruth Knüchel 1; Stefan Garczyk 1
1Pathologie, Uniklinik RWTH Aachen, Aachen, Deutschland
2Urologische Klinik, Klinikum der LMU München , München, Deutschland
Purpose: Non-muscle-invasive bladder cancer is characterized insu-
ciently. It is accepted that high-grade papillary tumors (pTaHG) develop
from a precedent low-grade (LG) lesion. Based on clinical data it is hy-
pothesized that pTaHG tumors might also develop de novo. In this study
we aimed to characterize potentially de novo pTaHG cancers by immuno-
histochemistry (IHC) and NGS, especially focussing on potential targeted
therapies.
Methods: 78 samples from 48 patients presenting with pTaHG cancer
without a history of previous or concomitant pTaLG or muscle-invasive
disease (44 pTaHG, 34 papillary pT1a/pT1HG samples) were analyzed for
protein expression of luminal and basal markers. e presence of genetic
alterations with therapeutic potential was studied by targeted sequencing
in a cohort of 23 samples from 23 patients (19 pTaHG/papillary pT1HG
tumors, four smooth muscle controls). For analysis only the exophytic tu-
mor area was considered.
Results: Potential de novo pTaHG/papillary pT1a/pT1HG tumors were
characterized by a luminal IHC-based phenotype (KRT20+: 74% (58/78),
GATA3+: 99% (77/78), ERbeta+: 96% (75/78), HER2 Dako score 3+: 28%
(22/78)), while lacking in basal marker expression in the majority of cas-
es (KRT5/6+: 3% (2/78), KRT14+: 9% (7/78)). At least one alteration in
genes potentially impacting the selection of targeted therapies, including
frequent alterations in genes encoding chromatin-modifying proteins
(e.g. KDM6A in 47%, ARID1A in 37% of cases), was detected in 95%
(18/19) of cases. Noteworthy, TP53 (21%) and FGFR3 (16%) mutational
rates were similar.
Conclusions: Potential de novo pTaHG tumors are luminal lesions char-
acterized by frequent alterations in genes encoding chromatin-modify-
ing proteins and a similar rate of TP53 and FGFR3 alterations. e vast
majority of cases harbored alterations in genes potentially impacting the
selection of targeted therapies.
Reference:
1. Pathologe (2019) 40(Suppl 2): 41. https://doi.org/10.1007/s00292-019-0616-1
Disclosure Statement: All contributing authors have no conicts of interest to
declare.
Vorträge
132
Checkmate 214 Post Hoc Analyses of Nivolumab Plus
Ipilimumab or Sunitinib in IMDC Intermediate/Poor-Risk
Patients with Previously Untreated Advanced Renal Cell
Carcinoma (ARCC) with Sarcomatoid Features (SRCC)
Marc-Oliver Grimm 1; David F. Mcdermott 2; Toni K. Choueiri 3;
Robert J. Motzer 4; Osvaldo Arén Frontera 5; Saby George 6;
Thomas Powles 7; Frede Donskov 8; Michael R. Harrison 9;
Jerónimo Rodríguez-Cid 10; Yuko Ishii 11; Brent Mchenry 11;
Brian I. Rini 12; Nizar M. Tannir 13
1University Hospital of Jena, Jena, Deutschland
2Beth Israel Deaconness Medical Center, Dana-Farber/Harvard Cancer Center,
Boston, MA, United States
3Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard
Medical School, Boston, MA, United States
4Memorial Sloan Kettering Cancer Center, New York, NY, United States
5Centro de Investigación Clínica Bradford Hill, Recoleta, Chile
6Roswell Park Cancer Institute, Bualo, NY, United States
7Barts Cancer Institute, Queen Mary University of London, Royal Free NHS Trust,
London, United Kingdom
8Aarhus University Hospital, Aarhus, Dänemark
9Duke Cancer Institute, Durham, NC, United States
10Centro Oncológico, Hospital Medica Sur, Mexico City Area, Mexico
11Bristol-Myers Squibb, Princeton, NJ, United States
12Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, United States
13University of Texas MD Anderson Cancer Center, Houston, TX, United States
Purpose: Patients (pts) with aRCC with sRCC have poor prognosis and
suboptimal outcomes with anti-VEGF targeted therapy. Nivolumab plus
ipilimumab (N+I) demonstrated superior objective response rate (ORR)
and overall survival (OS) vs sunitinib (S) in previously untreated pts with
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IMDC intermediate/poor (I/P)-risk, clear cell, advanced RCC in the
phase 3 CheckMate 214 trial.
Methods: We performed a post hoc exploratory analysis of N+I vs S in
CheckMate 214 sRCC pts. e presence of sarcomatoid features was as-
sessed by keyword search for “sarcomatoid” in pts with available local pa-
thology reports accompanying pretreatment tumor samples.
Results: 842 (77%) of 1096 intention-to-treat pts had local pathology re-
ports available, including 112 randomized pts with I/P-risk sRCC (N+I,
n=60; S, n=52). Baseline characteristics of sRCC pts were balanced be-
tween arms. Notably, 47% vs 53% of I/P-risk sRCC pts in the N+I and S
arms had baseline tumor PD-L1 expression ≥1%, which was higher than
in all I/P-risk pts (N+I, 26% vs S, 29%). In descriptive analyses performed
at a minimum follow-up of 30 months, conrmed ORR (56.7% [95% CI
43.2–69.4] vs 19.2% [95% CI 9.6–32.5]; P<0.001) and complete response
rate per investigator (RECIST v1.1; 18.3% vs 0%), OS (median [95% CI]
31.2 [23.0‒not estimable] vs 13.6 [7.7‒20.9] months; HR [95% CI], 0.55
[0.33‒0.90]; P<0.0155 ), and progression-free survival (median [95% CI]
8.4 [5.2–24.0] vs 4.9 [4.0‒7.0] months; HR [95% CI], 0.61 [0.38‒0.97];
P<0.03) per investigator were improved with N+I vs S in I/P-risk pts with
sRCC. No new safety signals were seen in sRCC pts.
Conclusions: In this post hoc descriptive subgroup analysis of Check-
Mate 214, N+I demonstrated promising ecacy and prolonged survival
vs S, with consistent safety, in untreated, I/P-risk, advanced clear cell RCC
with sarcomatoid features. Prospective studies of N+I that include pts
with sRCC are ongoing.
372
Apalutamide (APA) and Overall Survival (OS) in Patients (PTS)
with Nonmetastatic Castration-Resistant Prostate Cancer
(NMCRPC): Updated Results from The Phase 3 Spartan Study
Boris A. Hadaschik 1; Matthew R. Smith 2; Fred Saad 3; Simon Chowdhury 4;
Stéphane Oudard 5; Julie N. Gra 6; David Olmos 7; Paul N. Mainwaring 8;
Ji Youl Lee 9; Hiroji Uemura 10; Peter De Porre 11; Andressa Smith 12;
Ke Zhang 13; Angela Lopez-Gitlitz 14; Eric J. Small 15
1University of Duisburg-Essen, Essen, and Ruprecht-Karls University Heidelberg,
Heidelberg, Germany
2Massachusetts General Hospital Cancer Center and Harvard Medical School,
Boston, MA, USA
3Centre Hospitalier de l’Université de Montréal, Université de Montréal,
Montréal, Québec, Canada
4Guy’s, King’s and St. Thomas’ Hospitals, and Sarah Cannon Research Institute,
London, UK
5Georges Pompidou Hospital, Paris, France
6VA Portland Health Care System, Portland and Knight Cancer Institute, Oregon
Health & Science University, Portland, OR, USA
7Spanish National Cancer Research Centre (CNIO), Madrid and Hospitales
Universitarios Virgen de la Victoria y Regional de Málaga, Spain
8Centre for Personalized Nanomedicine, University of Queensland, Brisbane,
Australia
9St. Marys Hospital of Catholic University, Seoul, South Korea
10Yokohama City University Medical Center, Yokohama, Japan
11Janssen Research & Development, Beerse, Belgium
12Janssen Research & Development, Spring House, PA, USA
13Janssen Research & Development, San Diego, CA, USA
14Janssen Research & Development, Los Angeles, CA, USA
15Helen Diller Family Comprehensive Cancer Center, University of California
San Francisco, San Francisco, CA, USA
Purpose: In the Ph3 PBO-contr. SPARTAN study, APA with ongoing
ADT signi. improved metastasis-free survival (MFS) (HR, 0.28; 95% CI,
0.23-0.35; p < 0.001), time to symptomatic progress., and progress.-free
survival on 2nd therapy compared with PBO with ongoing ADT in pts with
nmCRPC. At the primary analysis for MFS, APA was associa. with im-
proved OS (HR, 0.70; 95% CI, 0.47-1.04; p = 0.07) and time to initiation of
cytotoxic chemotherapy. OS results were immature, with only 104 of 427
events (24%) required for the prespecied nal OS analysis. We report a
second interim analysis (IA2) for OS aer 285 events (65% of required
events).
Methods: Pts with nmCRPC and PSA doubling time of ≤ 10 mths were
random. 2:1 to APA (240 mg QD) or PBO, with ongoing ADT. e OS
eect of APA vs PBO was assessed using a group sequential testing pro-
cedure with O’Brien-Fleming-type alpha spending function. e required
p value for stati. signi. at IA2 was 0.0121. OS was analyzed by Kaplan-
Meier method and Cox model.
Results: At 41 mths’ med. follow-up and 285 OS events, APA was asso-
cia. w/ improved OS compared with PBO (HR, 0.75; 95% CI, 0.59-0.96;
p = 0.0197). e 4-yr OS rates for APA and PBO were 72.1% and 64.7%,
respect.. Aer unblinding the study and prior to IA2, 76 nonprogressing
PBO pts (19%) crossed over to open-label APA. At IA2, the proportion of
pts who received subsequent life-prolonging therapy was 68% in the PBO
group and 38% in the APA group. Rates of disconti. due to progressive
disease and AE were 34% and 14%, for the APA group, and 74% and 8%
for the PBO group. Rates of treatment-emergent AEs for APA at IA2 were
similar to the rates previously reported at IA1.
Conclusions: At IA2, APA was associa. w/ a 25% reduc. in risk of death
compared with PBO. is OS benet for APA was observed desp. cross-
over of PBO pts to APA and higher rates of subsequent life-prolonging
therapy for PBO pts. APA safety prole remained unchanged. ese re-
sults further support APA as a standard of care option for pts with high-
risk nmCRPC.
Reference:
1. ESMO Congress Barcelona 27 Sep-01 Oct 2019
690
Profound: Phase III Study of the Ecacy and Safety of
Olaparib versus Enzalutamide or Abiraterone Acetate in
Men with Metastatic Castration-Resistant Prostate Cancer
(mCRPC) and Homologous Recombination Repair Gene (HRR)
Alterations
S Feyerabend 1; M Hussain 2; J Mateo 3; K Fizazi 4; F Saad 5; N Shore 6;
SSandhu 7; K Chi 8; O Sartor 9; N Agarwal 10; D Olmos 11; A Thiery-Vuillemin 12;
P Twardowski 13; N Mehra 14; C Goessl 15; J Kang 15; J Burgents 16; W Wu 15;
AKohlmann 17; C Adelman 17; J De Bono 18
1Studienpraxis Urologie, Nürtingen, Deutschland
2Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Feinberg School of Medicine, Chicago, United States
3Vall d’Hebron Institute of Oncology, Barcelona, Spanien
4Institut Gustave Roussy, University of Paris Sud, Villejuif, Frankreich
5Centre Hospitalier de l’Université de Montréal/CRCHUM, Montreal, Kanada
6Carolina Urologic Research Center, Myrtle Beach, United States
7Peter MacCallum Cancer Centre, Melbourne, Australien
8BC Cancer Agency, Vancouver, Kanada
9Tulane University School of Medicine, New Orleans, United States
10Huntsman Cancer Institute, University of Utah (NCI-CCC), Salt Lake City,
United States
11Spanish National Cancer Research Centre (CNIO), Hospitales Universitarios
Virgen de la Victoria y Regional de Málaga, Madrid, Spanien
12CU-PH Medical Oncology Unit, CHU Besançon, Besançon, Frankreich
13City of Hope National Medical Center, Duarte, United Kingdom
14Radboud University Medical Center, Nijmegen, Netherlands Antilles
15AstraZeneca, Gaithersburg, United States
16Merck & Co., Inc, Kenilworth, United States
17AstraZeneca, Cambridge, United Kingdom
18The Institute of Cancer Research and Royal Marsden, London, United Kingdom
Purpose: mCRPC is a molecularly heterogenous disease. Tumors in a
sizable proportion of patients with mCRPC harbor loss-of-function al-
terations in genes involved in HRR (egBRCA1,BRCA2andATM). HRR
alterations have been associated with increased sensitivity to the PARP in-
hibitor olaparib in mCRPC. e PROfound study (NCT02987543) evalu-
ates olaparib ecacy and safety versus either enzalutamide or abiraterone
acetate, in mCRPC patients with an HRR alteration.
Methods: PROfound is a randomized, open-label, Phase III study in
men with mCRPC, for whom prior new hormonal agent treatment for
metastatic prostate cancer and/or CRPC had failed. Eligible patients had
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts72
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2018
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2018
a qualifying tumor HRRm in 1 of 15 genes, prospectively and centrally
determined in tumor tissue using an investigational next-generation se-
quencing test (Foundation Medicine, Inc.). Two cohorts were enrolled:
Cohort A (n=245) included patients with alterations in BRCA1, BRCA2
or ATM; Cohort B included patients with an alteration in 12 other HRR
genes (n=142). Patients were randomized (2:1) to olaparib tablets (300mg
bid) or physicians choice of either enzalutamide (160 mg orally od) or
abiraterone acetate (1000 mg orally od + 5 mg bid prednisone). Treatment
continued until radiographic progression (assessed by blinded indepen-
dent central review or lack of treatment tolerability. e primary endpoint
of radiographic progression-free survival (rPFS) in Cohort A was assessed
by BICR using RECIST 1.1 and PCWG3 criteria and analyzed via strati-
ed log-rank test.
Results and conclusions: e abstract will be updated with results and
conclusions pending data availability.
Funding Source: AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of
Merck & Co., Inc., Kenilworth, NJ, USA
Poster
147
Prediction of Response Rate and Long-Term Survival in
Polychemotherapy for Metastatic Penile Cancer by the
Glasgow Prognostic Score
Desiree Louise Dräger; Tim Buchholz; Sophie Groh; Oliver Hakenberg
Urologische Universitätsklinik, Universitätsmedizin Rostock, Rostock,
Deutschland
Purpose: e Glasgow Prognostic Score (GPS) is dened by a combina-
tion of elevated C-reactive protein serum level (> 10 mg/L) and of hypoal-
buminemia (< 35 g/L). It is considered in a variety of tumor entities as an
independent prognostic marker, which predicts the biological behavior of
malignant tumors. e survival rates for metastatic penile carcinoma are
low. ere is increasing evidence that patient-related prognostic factors,
such as a persistent systemic inammatory response, lead to low survival
rates in tumor patients. e aim of the current study was to clarify the
value of GPS in metastatic penile carcinoma in terms of response rate and
long-term survival.
Methods: e correlation of GPS and long-term survival and response
rate was studied in 68 patients with metastatic penile carcinoma. For this
purpose, a score of C-reactive protein and albumin was determined pri-
or to systemic treatment in order to correlate this consecutively with the
follow-up.
Results: e survival and response of GPS-1 patients was signicantly
worse than that of GPS-0 patients (p = 0.006) and the survival and re-
sponse of GPS-2 patients was signicantly worse than that of GPS-1 pa-
tients (p <0.0001). Multivariate analysis showed that GPS (p <0.0001),
tumor stage (p = 0.004), venous and lymph vessel invasion (p = 0.011)
were factors that were independently associated with a worse prognosis.
Conclusions: e GPS can stratify the clinical outcome of penile cancer
and can be used as a prognostic indicator.
Disclosure Statement: none
148
Quantication of Lymphedema of the Lower Extremity and
the External Genitals After Inguinal Lymphadenectomy in
Penile Cancer Patients and Its Impact on the Quality of Life
Desiree Louise Dräger; Eva-Maria Fritz; Julia Nolting; Maria Woehl;
Oliver Hakenberg
Urologische Universitätsklinik, Universitätsmedizin Rostock, Rostock,
Deutschland
Purpose: Lymphedema of the lower extremity and the external genitals as
a result of penile cancer treatment is a chronic disease that can signicant-
ly impair the quality of life. In the present study, various aspects of lymph-
edema associated with penile cancer were examined, including measure-
ment methods, denitions, risk factors and, in particular, the eects on
the physical, psychological and emotional well-being of aected men.
Methods: In a retrospective cohort study, we investigated the relationship
between lymphedema, quality of life and surgical factors (radical vs. mod-
ied lymphadenectomy, LND). A total of 76 men, surgically treated for
penile cancer, were evaluated at least 1 year aer LND.
Results: In 29% of men lymphedema was detected (leg volume dierence
> 200cm³). Aected men have a reduced self-esteem due to a distorted
body image. Negative emotions reported include anxiety, frustration, sad-
ness, anger, anxiety, and reduced self-esteem.
Conclusions: Lymphedema as a result of penile cancer treatment contin-
ues to be a signicant quality of life problem with consequences for phys-
ical, mental and emotional well-being. e development of lymphedema
leads to physical impairment, including impaired function, diminished
strength, fatigue and pain in the aected limb.
Disclosure Statement: none
155
Traumatic Spinal Cord Injury Confers Bladder Cancer Risk:
Lessons from a Comparison of Clinical Data with the National
Database
Ralf Böthig 1; Ines Kurze 2; Kai Fiebag 1; Christian Tiburtius 1; Birgitt Kowald 3;
Sven Hirschfeld 4; Roland Thietje 4; Albert Kaufmann 5; Wolfgang Schöps 6;
Michael Zellner 7; Holger Böhme 8; Thura Kadhum 9; Klaus Golka 9
1BG Klinikum Hamburg, Abt. Neuro-Urologie, Querschnittgelähmten-Zentrum,
Hamburg, Deutschland
2Zentralklinik Bad Berka, Klinik für Paraplegiologie und Neuro-Urologie, Bad
Berka, Deutschland
3BG Klinikum Hamburg, Biomechanisches Labor, Hamburg, Deutschland
4BG Klinikum Hamburg, Querschnittgelähmten-Zentrum, Hamburg,
Deutschland
5Kliniken Maria Hilf GmbH, Zentrum für Kontinenz & Neuro-Urologie,
Mönchengladbach, Deutschland
6Praxis Urologie Sankt Augustin
7Johannesbad Fachklinik, Abt. Urologie und Neuro-Urologie, Bad Füssing,
Deutschland
8Asklepios Klinik Barmbek, Klinik für Urologie, Hamburg, Deutschland
9Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Dortmund,
Deutschland
Purpose: Life expectancy for people with traumatic spinal cord injury
(TSCI) is increasing due to advances in treatment methods and in neu-
ro-urology. us, developing urinary bladder cancer (UBC) is gaining
importance.
Methods: Single-center retrospective evaluation of consecutive in- and
out-patient data with spinal cord injury between January 1, 1998 and De-
cember 31, 2018 was carried out and data were compared with publicly
available UBC data of the German population from the Center for Cancer
Registry Data of the Robert Koch-Institute.
Results: A total of 37 (4 female, 33 male) out of 7004 patients with TSCI
were diagnosed with histologically proven urinary bladder cancer. Medi-
an follow-up of TSCI patients with UBC was 85 months. Median age at
bladder cancer diagnosis was 54.0 years, which is well below the average
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2018
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2018
for bladder cancer cases in the general population in Germany (male: 73,
female: 77 years).
All but two patients had a latency period between the onset of TSCI and
tumour diagnosis of more than 10 years (median: 30.0 years).
Of the 37 patients, 30 (81%) had muscle invasive bladder cancer at ≥T2 at
the time of diagnosis, 27 out of 37 patients showed a histologically poorly
dierentiated G3 carcinoma. Both frequency distributions dier signi-
cantly between TSCI patients (p <0.0001 each) and the normal German
population.
Median survival for all patients was 12.0 months (transitional cell carci-
noma (n=31) 13 months; squamous cell carcinoma (n=5) 4 months, p =
0.0039). e prognosis of the 24 cystectomized patients was 15.0 months
and thus signicantly better than in those without cystectomy (p = 0.0148)
32 patients suered from urodynamically conrmed neurogenic detrusor
overactivity while 5 patients (all male) had detrusor acontractility.
Long-term suprapubic or indwelling catheterization was found in only 8
patients for a total of only 5.09% (median: 15.5 months) of the latency of
all patients.
Conclusions: e results indicate that the neurogenic bladder caused by
traumatic SCI itself is the main risk factor for bladder cancer.
216
Clinical Outcome of PSMA-Guided Radiotherapy for Patients
with Oligorecurrent Prostate Cancer
Katharina Sprute 1; Stefan A. Koerber 2, 3, 4; Clemens Kratochwil 1, 5;
Matthias F. Haefner 2, 3, 4; Henrik Rathke 1; Klaus Herfarth 2, 3, 4, 6; Klaus
Kopka 7, 8; Tim Holland-Letz 9; Uwe Haberkorn 1, 5; Juergen Debus 2, 3, 4, 6, 8, 10;
Frederik L. Giesel 1, 5, 8
1Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg,
Deutschland
2National Center for Tumor diseases (NCT), Heidelberg, Deutschland
3Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Deutschland
4Department of Radiation Oncology, Heidelberg University Hospital,
Heidelberg, Deutschland
5Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center
(DKFZ), Heidelberg, Deutschland
6Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation
Oncology, Heidelberg University Hospital, Heidelberg, Deutschland
7Division of Radiopharmaceutical Chemistry, German Cancer Research Center
(DKFZ), Heidelberg, Deutschland
8German Cancer Consortium (DKTK), Heidelberg, Deutschland
9Department of Biostatistics, German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
10Clinical Cooperation Unit Radiation Oncology, German Cancer Research
Center (DKFZ), Heidelberg, Deutschland
Purpose: First line treatment of patients with recurrent, metastatic pros-
tate cancer is a combination of hormone therapy with or without chemo-
therapy/ abiraterone, as a systemic, palliative treatment. A new perspec-
tive is given by PSMA-PET/CT-guided irradiation, which demonstrated
promising ecacy in recent trials. e current study aimed to classify the
type and localization of metastases aer primary treatment and its clinical
outcome.
Methods: Between 2011 and 2019, 86 patients (mean age of 69 years) with
recurrent, oligometastatic prostate cancer received a PSMA-PET/CT fol-
lowed by a precise irradiation of their metastases. 60 patients underwent
a clinical follow-up including a quality of life status. Data were analyzed
retrospectively regarding the region of relapse and the primary endpoints
overall survival (OS), biochemical progression free survival (bPFS) and
androgen deprivation therapy (ADT)-free survival.
Results: e median follow- up was 24 months (range 4-72). According
to the dAmico risk classication, 90.7% of all patients were categorized as
high-risk. A median amount of 1.0 metastases per patient could be identi-
ed. In total, 49.4% of the metastases were considered as metastases of the
bone, 34.1% were nodal metastases within and 16.5% nodal metastases
outside of the pelvis. A 2-year OS rate of 95.7% and a 2-year bPFS rate
of 85.1% were calculated. e data analysis revealed a mean ADT- free
time of 15.9 months (range 3-40). Biochemical response was detected in
83.3% of the cohort. If a progress monitoring via PSMA-PET/CT was im-
plemented, the standard uptake value (SUV) of the irradiated metastases
was reduced signicantly.
Conclusions: PSMA-guided radiotherapy is a promising, novel therapeu-
tic approach for oligorecurrent prostate carcinoma to extent OS and bPFS
in comparison to systemic therapy and should be more considered in the
recurrent situation. However, prospective, randomized trials are necessary
to conrm and validate the analyzed data with a larger cohort of patients.
295
Clinical Outcomes According to PD-L1 Status and Age in the
Prospective International Saul Study of atezolizumab (ATEZO)
for Locally Advanced or Metastatic Urothelial Carcinoma (UC)
or Non-UC of the Urinary Tract
Friedemann Zengerling 1; Cora N. Sternberg 2; Axel S. Merseburger 3;
Ernest Choy 4; Daniel Castellano 5; Fernando Lopez-Rios 6; Nick James 7;
Giuseppe L. Banna 8; Ugo De Giorgi 9; Cristina Masini 10; Aristotelis
Bamias 11; Xavier Garcia del Muro 12; Thomas Powles 13; Ignacio Duran 14, 15;
Craig Gedye 16; Marija Gamulin 17; Lajos Geczi 18; Sabine de Ducla 19;
Simon Fear 19; Yohann Loriot 20
1Department of Urology, University Hospital Ulm, Ulm, Deutschland
2Weill Cornell Medicine, New York, NY, United States
3Department of Urology, Campus Lübeck, University Hospital Schleswig-
Holstein, Lübeck, Deutschland
4CREATE Centre, Section of Rheumatology, Division of Infection and Immunity,
Cardi University School of Medicine , Cardi, United Kingdom
5Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid,
Spanien
6Hospital Universitario HM Sanchinarro, Madrid, Spanien
7Institute of Cancer and Genomic Services, University of Birmingham, and
Cancer Centre, Queen Elizabeth Hospital, Birmingham, United Kingdom
8Cannizzaro Hospital, Catania, Italien
9Istituto Scientico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS,
Meldola, Italien
10Medical Oncology Unit, AUSL-IRCCS Reggio Emilia, Reggio Emilia, Italien
11National and Kapodistrian University of Athens, Alexandra Hospital, Athens,
Griechenland
12Institut Catala d’Oncologia, IDIBELL, Barcelona, Spanien
13Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary
University of London, St Bartholomews Hospital, London, United Kingdom
14Hospital Universitario Virgen del Rocio, Seville, Spanien
15Hospital Universitario Marques de Valdecilla, Santander, Spanien
16Calvary Mater Newcastle, Waratah, NSW, Australien
17University Hospital Centre ‘Zagreb’, Zagreb, Kroatien
18National Institute of Oncology, Budapest, Ungarn
19F. Homann-La Roche Ltd, Basel, Schweiz
20Department of Cancer Medicine and INSERM U981, Université Paris-Sud,
Université Paris-Saclay, Gustave Roussy, Villejuif, Frankreich
Purpose: Atezo, a monoclonal antibody targeting PD-L1, is an ap-
proved therapy for locally advanced/metastatic UC based on IMvig-
or210 and IMvigor211 phase II and III trials. e single-arm SAUL study
(NCT02928406) with a broader patient (pt) population demonstrated
median overall survival (OS) of 8.7 months and a safety prole consistent
with previous atezo trials.
Methods: Pts with locally advanced/metastatic UC or non-UC of the uri-
nary tract received atezo 1200 mg every 3 weeks until disease progression
or unacceptable toxicity. Populations excluded from IMvigor211 (renal
impairment, ECOG PS 2, treated asymptomatic CNS metastases, stable
controlled autoimmune disease, concomitant steroids, HIV positive, non-
UC) were eligible. e primary endpoint was safety; OS and overall re-
sponse rate (ORR) were secondary endpoints. Predened subgroup anal-
yses included outcomes according to PD-L1 status (VENTANA SP142)
and age in the overall population (and the IMvigor211-like subgroup for
PD-L1).
Results: Between Nov 2016 and Mar 2018, 1004 pts were enrolled; 997
received atezo. Median (95% CI) OS was overall IC 0/1 vs IC 2/3: 7.9 (6.8–
9.1) vs. 11.6 (8.8–18.8); IMvigor211-like IC 0/1 vs 2/3: 9.0 (7.8–10.4) vs
14.5 (9.5–18.8). ORR (95% CI) was overall IC 0/1 vs IC 2/3: 10% (8–13) vs
21% (16–26); IMvigor211-like IC 0/1 vs 2/3: 10% (7–13) vs 23% (17–30).
Treatment response was observed in all age groups (ORR [95% CI], ≥65 y:
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts74
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2018
Index
2018
14% [12–17]; ≥75 y: 13% [9–18]; ≥80 y: 8% [3–16]). Incidences of grade
≥3 treatment-related adverse events were similar irrespective of PD-L1
status (overall IC 0/1 vs 2/3: 11% vs 16%; IMvigor211-like IC 0/1 vs 2/3:
11% vs 15%) or age (≥65 y: 13%; ≥75 y: 12%; ≥80 y: 10%).
Conclusions: OS and ORR appear more favorable in IC2/3 vs IC0/1 sub-
groups (overall and in the IMvigor211-like population). Atezo was eec-
tive and well tolerated across subgroups including elderly pts.
Reference:
1. Sternberg et al. ASCO 2019
323
Association Between Depth of Response (DepOR) and
Overall Survival (OS): Exploratory Analysis of Nivolumab +
Ipilimumab (N+I) vs Sunitinib (S) in Patients with Previously
Untreated Advanced Renal Cell Carcinoma (ARCC) in
Checkmate 214
Viktor Gruenwald 1; Toni K. Choueiri 2; Brian I. Rini 3; Thomas Powles 4;
Saby George 5; Marc-Oliver Grimm 6; M. Brent Mchenry 7;
Matthew Maurer 7; Robert J. Motzer 8; Hans J. Hammers 9; Nizar M. Tannir 10;
Laurence Albiges 11
1Interdisciplinary Genitourinary Oncology at the West-German Cancer Center,
Clinic for Internal Medicine (tumor research) and Clinic for Urology, University
Hospital Essen, Essen, Deutschland
2Department of Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham
and Womens Hospital, and Harvard Medical School, Boston, United States
3Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer
Institute, Cleveland, United States
4Department of Medicine, Barts Cancer Institute, Queen Mary University of
London, Royal Free NHS Trust, London, United Kingdom
5Department of Medicine, Roswell Park Cancer Institute, Bualo, United States
6Department of Urology, Jena University Hospital, Jena, Deutschland
7Bristol-Myers Squibb, Princeton, United States
8Department of Medicine, Memorial Sloan Kettering Cancer Center, New York,
United States
9Department of Medicine, UT Southwestern – Kidney Cancer Program, Dallas,
United States
10Department of Genitourinary Medical Oncology, University of Texas MD
Anderson Cancer Center, Houston, United States
11Department of Medical Oncology, Gustave Roussy, Villejuif, Frankreich
Purpose: DepOR (max % reduction from baseline in sum of target lesion
diameters) has shown prognostic value for long-term survival in multiple
malignancies. Among aRCC intention-to-treat patients (pts) in Check-
Mate 214 superior ecacy was recently shown with N+I over S at 30-mo
min follow-up. e relationship between DepOR and OS was evaluated in
CheckMate 214 to determine a potential DepOR threshold predictive of
long-term OS with N+I.
Methods: Pts were randomized 1:1 to N+I (3 mg/kg + 1 mg/kg IV) Q3W
for 4 doses, followed by N (3 mg/kg IV) Q2W, or S 50 mg/day orally for
4 wk (6-wk cycles). An exploratory analysis of OS by DepOR quartiles
was conducted (Q0, no reduction; Q1, >0–≤25%; Q2, >25–≤50%; Q3,
>50–≤75%; Q4, >75–≤100%).
Results: Of 550 and 546 pts randomized to N+I or S, 479 and 459, re-
spectively, had postbaseline target lesion measurements. Among Q0 pts,
median OS was longer and OS probabilities were notably higher with N+I
vs S. Overall, greater DepOR was associated with improved OS in both
arms. e OS probability HR (95% CI) vs Q0 was 0.63 (0.43–0.93) for Q1,
0.65 (0.42–1.01) for Q2, 0.22 (0.13–0.38) for Q3, and 0.18 (0.11–0.32) in
the N+I arm (all P<0.0001). e OS probability vs Q0 progressively de-
creased with greater DepOR in arm S; however, N+I pts with >50–≤75%
(Q3) tumor reduction had similar OS benets as those with >75% (Q4)
reduction, whereas only Q4 pts achieved comparable OS with S (203/550
[37%] N+I vs 46/546 [8%] S randomized pts). Receiver operating charac-
teristic analysis supported a >50% DepOR threshold for greatest OS bene-
t with N+I. Additional analyses of the relationship between DepOR and
outcomes across arms will be presented.
Conclusions: e relationships between DepOR and OS are distinct for
N+I vs S, with a greater percentage of N+I pts having prolonged OS. Sim-
ilar notable OS benets in N+I DepOR Q3 and Q4 suggest that a DepOR
threshold >50% may be a useful indicator of potential for long-term sur-
vival with N+I in aRCC pts. Prospective analyses to determine clinical
applications are needed. Previously presented at Esmo 2019, Fpn 950P,
Grünwald et al. Reused with permission.
Disclosure Statements:
Viktor Grünwald reports grants and personal fees from Pzer; grants, personal
fees and non-nancial support from Bristol-Myers Squibb; personal fees and
non-nancial support from Roche; personal fees and non-nancial support from
Novartis; personal fees and non-nancial support from EISAI; grants, personal
fees, and non-nancial support from Ipsen; and grants and personal fees from
EUSA Pharm, during the conduct of the study and grants, personal fees, non--
nancial support, and stock ownership from MSD; grants from Novartis; grants,
personal fees, and stock ownership from AstraZeneca; grants, personal fees,
non-nancial support, and stock ownership from Bristol-Myers Squibb; personal
fees and non-nancial support from Merck Serono; personal fees from Roche;
personal fees from Pzer; personal fees from Lilly; personal fees and non-nancial
support from PharmaMar; personal fees from Nanobiotix; and personal fees from
Janssen, outside the submitted work.
Toni K. Choueiri reports research funding (institutional and personal) from
AstraZeneca, Alexion, Bayer, Bristol-Myers Squibb/ER Squibb and Sons LLC,
Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech,
Roche, Roche Products Limited, F. Homann-La Roche, GlaxoSmithKline, Lilly,
Merck, Novartis, Peloton, Pzer, Prometheus Labs, Corvus, Calithera, Analysis
Group, Sano/Aventis, and Takeda; honoraria from AstraZeneca, Alexion, Sano/
Aventis, Bayer, Bristol-Myers Squibb/ER Squibb and Sons LLC, Cerulean, Eisai,
Foundation Medicine Inc., Exelixis, Genentech, Roche, Roche Products Limited,
F. Homann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pzer, EMD
Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, National Comprehensive
Cancer Network, Analysis Group, Michael J. Hennessy (MJH) Associates, Inc
(healthcare communications company with several brands such as OnClive, Peer-
View and PER), L-path, Kidney Cancer Journal, Clinical Care Options, Platform
Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology,
New England Journal of Medicine, Lancet Oncology, Heron erapeutics, and
Lilly; consulting or advisory role with AstraZeneca, Alexion, Sano/Aventis, Bayer,
Bristol-Myers Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation
Medicine Inc., Exelixis, Genentech, Heron erapeutics, Lilly, Roche, GlaxoSmith-
Kline, Merck, Novartis, Peloton, Pzer, Emd Serono, Prometheus Labs, Corvus,
Ipsen, Up-to-Date, National Comprehensive Cancer Network, and Analysis Group;
patents, royalties or other intellectual properties: International Patent Application
No. PCT/US2018/12209, titled “PBRM1 Biomarkers Predictive of Anti-Immune
Checkpoint Response,” led January 3, 2018, claiming priority to U.S. Provisional
Patent Application No. 62/445,094, led January 11, 2017, and International Patent
Application No. Pct/US2018/058430, titled “Biomarkers of Clinical Response and
Benet to Immune Checkpoint Inhibitor erapy,” led October 31, 2018, claim-
ing priority to U.S. Provisional Patent Application No. 62/581,175, led November
3, 2017.
Brian I. Rini reports research funding to institution from Pzer, Merck, GNE/
Roche, Peloton, Aveo, AstraZeneca, and Bristol-Myers Squibb; consulting fees
from Bristol-Myers Squibb, Pzer, GNE/Roche, Aveo, Novartis, Synthorx,
Peloton, Compugen, Merck, Corvus, and Exelixis; and stock holding with PTC
erapeutics.
omas Powles reports research funding from AstraZeneca/MedImmune and
Roche/Genentech; consulting/advisory roles with Genentech/Roche, Bristol-Myers
Squibb, Merck, Novartis, and AstraZeneca; honoraria from Roche/Genentech,
Bristol-Myers Squibb, and Merck; and other relationships with Ipsen and Bristol-
Myers Squibb.
Saby George reports consulting/advisory roles with Bayer, Bristol-Myers Squibb,
Novartis, Exelixis, Janssen, Corvus, Genentech, Sano/Genzyme, Pzer, and EMD
Serono; and grants from Acceleron, Merck, Agensys, and Eisai.
Marc-Oliver Grimm reports research funding and consulting/advisory fees
from Novartis; research funding, consulting/advisory fees, and honoraria from
Bristol-Myers Squibb; consulting/advisory fees and honoraria from Pzer, Bayer
HealthCare, Sano Aventis, AstraZeneca, MSD, Janssen Cilag, and ONO Pharma-
ceutical; honoraria from Astellas, Hexal, Apohepha, Ipsen Pharma, and Medac;
consulting/advisory fees from Intuitive Surgical and Amgen, outside the submitted
work.
M. Brent McHenry reports employment with and stock ownership in Bristol-
Myers Squibb.
Matthew Maurer reports employment with and stock ownership in Bristol-Myers
Squibb.
Robert J. Motzer reports research funding paid to institution from Bristol-Myers
Squibb, Pzer, Novartis, Eisai, Exelixis, and Genentech/Roche; and consultancy
roles with Bristol-Myers Squibb, Pzer, Novartis, Eisai, Exelixis, Genentech/Roche,
DKK_Abstracts_001-246.indd 74 11/02/20 12:05 PM
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 75
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2018
Merck, Incyte, and Lilly.
Hans J. Hammers reports clinical trial support and advisory board roles with
Bristol-Myers Squibb and Merck; and advisory board roles with Pzer, Exelixis,
Armo Biosciences, and Novartis.
Nizar M. Tannir reports research funding and advisory board roles with Bris-
tol-Myers Squibb, Pzer, Novartis, and Exelixis Inc; research funding from Cali-
thera Bioscience; advisory board roles with Nektar erapeutics, Oncorena, and
Eisai Medical Research; and a speakers bureau role with ONO Pharmaceutical.
Laurence Albiges reports consulting (by institution) for Pzer, Novartis,
Bristol-Myers Squibb, Ipsen, Roche, MSD, and AstraZeneca.
324
Nora: Real World Evidence in Renal Cell Carcinoma; A
National, Prospective, Non-Interventional Study in Patients
with Advanced/Metastatic Renal Cell Carcinoma Starting 1st
Line Nivolumab and Ipilimumab Combination Therapy or
Nivolumab Monotherapy After Prior Therapy
Harald Müeller-Huesmann 1; Jens Bedke 2; Viktor Grünwald 3; Hanjo Belz 4;
Martin Bögemann 5; Martin Herber 6; Eyck von der Heyde 7; Philipp Ivanyi 8;
Albrecht Kretzschmar 9; Martin Schostak 10; Wolfgang Schultze-
Seemann 11; Marc-Oliver Grimm 12
1Department of Internal Medicine, Hematology and Oncology
Brüderkrankenhaus St. Josef, Paderborn
2Department of Urology, Eberhard Karls University, Tübingen
3Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, University
Hospital Essen, Essen
4Zeisigwaldkliniken, Chemnitz
5University Hospital Muenster, Muenster
6Bristol-Myers-Squibb GmbH & Co. KGaA, München
7Studienzentrum am Raschplatz, Hannover
8Department of Hematology, Hemostasis, Oncology and Stem Cell
Transplantation, Hannover Medical School, Hannover
9MVZ Mitte Onkologische Schwerpunktpraxis, Leipzig
10Department of Urology and Pediatric Urology, University Hospital Magdeburg,
Magdeburg
11Department of Urology, Medical Center - University of Freiburg, Faculty of
Medicine, University of Freiburg, Freiburg
12Department of Urology, Jena University Hospital, Jena
Purpose: e pivotal Ph3 trials CM 214 (NCT02231749) and CM 025
(NCT01668784) showed long term overall survival benet for patients
with advanced/metastatic RCC treated with nivolumab + ipilimumab
combination therapy compared to sunitinib and for nivolumab alone vs.
everolimus. Real world data is needed to further evaluate the eectiveness
and tolerability in routine clinical care, as well as the quality of life associ-
ated with the treatment in a broader patient population.
Materials: NORA (NCT02940639) is an ongoing, non-interventional
study (NIS) in Germany. Overall, 490 adult patients diagnosed with ad-
vanced/metastatic RCC, who start a new systemic 1st line therapy with
nivolumab + ipilimumab with intermediate/poor risk (cohort-2, n=260)
or nivolumab aer prior therapy (cohort-1, n=230) according to market-
ing authorization in Germany, will be enrolled. Patients are followed for
5 years from treatment initiation until death, withdrawal of consent, loss
to follow-up or end of study. e primary endpoint is overall survival.
Secondary endpoints include progression free survival, response rates, ad-
verse events (AE), AE management and patient reported outcomes with
EQ-5D and FKSI19.
Results: At the September 30th 2019 data cut, 36 months aer start of
enrollment, interim data of 233 patients of cohort-1 describe baseline
characteristics and outcome of patients with a minimum follow-up of 6
months. e data also shows demographic and disease characteristics,
ECOG performance status and patient reported outcomes for 1st line pa-
tients documented until data cut.
Conclusion: We provide the rst eectiveness data of the NORA obser-
vational study in patients treated with nivolumab monotherapy in routine
care in Germany. Furthermore, information about baseline characteristics
in 1st line patients and the management of immune related adverse events
in clinical practice is shown. Taken together, these data give valuable in-
sight in the current treatment landscape and outcome in patients with ad-
vanced/metastatic RCC.
326
Successful Targeting of the Warburg Eect in Prostate
Cancer by Novel 1,4-Naphthoquinone Sulphomethylene
Carbohydrate Conjugates
Tobias Busenbender 1; Sergey Dyshlovoy 1, 2; Moritz Kaune 1;
Jessica Hauschild 1; Dmitry N. Pelageev 3; Valentin A. Stonik 3;
Markus Gräfen 2; Carsten Bokemeyer 1; Gunhild von Amsberg 1, 2
1Zentrum für Onkologie, II. Medizinische Klinik und Poliklinik (Onkologie,
Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie,
Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
2Martini-Klinik Prostate Cancer Center, Universitätsklinikum Hamburg-
Eppendorf, Hamburg, Deutschland
3G.B. Elyakov Pacic Institute of Bioorganic Chemistry, Far Eastern Branch
Russian Academy of Science, Vladivostok, Russland
Purpose: e ability of prostate cancer (PCa) cells to consume large
amounts of glucose due to overexpression of GLUT11 (Warburg eect)
can be used to enhance selectivity of anticancer drugs by their conjugation
to carbohydrates. 1,4-naphtoquinones exhibit cytotoxic eects by exerting
oxidative stress on cancer cells.2 Here, we characterize a series of novel
semi-synthetic molecules containing a 1,4-naphthoquinone conjugated
with glucose via S-CH2 bond.
Methods: A cytotoxicity screen was performed for the 34 novel com-
pounds in 22Rv1 cells by MTT assay. e two most active compounds
were evaluated in human PCa cells, as well as non-malignant cells to
conrm selectivity. Apoptosis induction, mitochondrial damage, oxida-
tive stress and glucose uptake were assessed by Western Blot and FACS
analysis.
Results: Two promising derivatives with IC50s of low micromolar
concentrations and high selectivity for PCa cells were identied in the
screen. Glucose depletion in media resulted in increased cytotoxicity
of the compounds, while GLUT1-inhibitors antagonized these eects,
suggesting a GLUT1-mediated uptake of the derivatives. Up-regulation of
cleaved caspase-3, cleaved PARP and Bax indicate an apoptotic character
of drug-induced cell death. At the same time, pro-survival pathways
(Bcl-2, Survivin) were suppressed under treatment. e compounds
reduced mitochondrial membrane potential, increased ROS levels and
the antioxidant N-acetylcysteine rescued treated cells from cell death,
suggesting oxidative stress to contribute to the cytotoxic activity. Strong
synergistic eects were observed in combination with PARP inhibitors.
Conclusions: We identied two novel compounds exhibiting potent ac-
tivity and selectivity in human PCa cells due to GLUT1-mediated uptake.
e mode of action comprises caspase-dependent apoptosis, suppression
of pro-survival processes and induction of oxidative stress. Eects on AR-
and MAPK-signaling, cancer cell proteome and autophagy are currently
investigated.
References:
1. Pertega-Gomez et al. J. Pathol 2015
2. Wellington RSC 2015
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts76
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2018
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2018
335
Survival Improvement in Metastatic Renal Cell Carcinoma
(MRCC) Patients Over Time: Do Elderly Patients Participate?
Hendrik Eggers 1; Viktor Grünwald 2; Linda Rudolph 1;
Maria-Louisa Tiemann 1; Christoph Reuter 1; Ganser Arnold 1;
Philipp Ivanyi 1
1Hannover Medical School, Department of Hematology, Hemostasis, Oncology
and Stem Cell Transplantation, Hannover Medical School, Hannover, Hannover,
Deutschland
2Essen University Hospital, Interdisciplinary Genitourinary Oncology at the
West-German Cancer Center, Clinic for Internal Medicine (Tumor research) and
Clinic for Urology, Essen, Deutschland
Purpose: e incidence of RCC is increasing and prognosis of mRCC
is still limited. However, new approaches have changed our therapeutic
landscape dramatically over the last two decades and overall survival (OS)
for mRCC is improving. Nonetheless, little is known about the outcome of
elderly mRCC patients. erefore, this monocentric retrospective analysis
addresses changes in overall survival between treatment periods and age
groups.
Methods: Patients with mRCC treated at Hannover Medical School from
01/2003 - 12/2018 were identied by retrospective chart review. Treat-
ment periods were dened from 01.01.2003 – 31.12.2009 (Period 1) and
01.01.2010 – 31.12.2018 (Period 2). Age groups were dened according
to WHO (age <61 years = not old, age 61-75 = older, age >76 = old). De-
scriptive statistics, Kaplan-Meier analysis and logistic regression were ad-
ministered.
Results: Overall, 314 patients showed a median OS of 40.1 months (95%-
CI: 32.8-47.4 month). Median OS is signicantly longer for patients
treated in period 2 vs. period 1 (59.1 vs. 35.1 months, p=0.003). Median
OS does not dier between not old vs. older and older vs. old. Subgroup
analysis of age groups within treatment periods showed no dierence, but
increase of median OS was more profound in age group old vs older com-
paring treatment periods (period 1 older 36.7, period 1 old 18.8, period 2
older 59.1, period 2 old 45.7 months).
Conclusions: While the increase in OS between treatment periods might
reect the advance of our therapeutic armamentarium, there is no dier-
ence in OS comparing age groups. Improvement of OS was comparable
between age groups, but with the largest increase in median OS across
treatment periods. Surprisingly, the old seem to prot particularly.
337
Prognostic Role of Docetaxel-Induced Reduction of Free
Testosterone Serum Levels in Metastatic Prostate Cancer
Patients
Paula Kappler 1; Michael Morgan 2; Philipp Ivanyi 1; Arnold Ganser 1;
Christoph Reuter 1
1Hämatologie, Hämostaseologie, Onkologie & Stammzelltransplanation,
Medizinische Hochschule Hannover, Hannover, Deutschland
2Experimentelle Hämatologie, Medizinische Hochschule Hannover, Hannover
Purpose: We have recently demonstrated that carboplatin plus weekly
docetaxel is eective in docetaxel-refractory prostate cancer (PC) and in-
terferes with testosterone biosynthesis (Reuter et al.; Oncol Res & Treat.
2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monother-
apy on free and total testosterone (fT, TT) serum levels and the prognostic
role of fT and TT were analyzed in mPC patients.
Methods: 59 consecutive mPC patients were treated with at least two cy-
cles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until
disease progression, occurrence of intolerable adverse eects or comple-
tion of the planned cycle number. Ecacy measures were done following
PCWG2 recommendations. FT and TT were measured before and during
chemotherapy.
Results: At the current analysis, the median follow-up time was 20.8
months. Response of prostate-specic antigen (PSAR; ≥50% PSA reduc-
tion) was observed in 39/59 (66.1%) and 11/37 (29.7%) patients with
measurable disease exhibited a partial remission (PR). Median progres-
sion-free survival (PFS) for all patients was 7.8 months (CI 95% 3.8, 11.8)
and median overall survival (OS) was 25.1 months (CI 95% 17.6, 32.7).
e most common reversible grade 3/4 toxicity was leukopenia/neutrope-
nia (29.3/34.5%). Median fT and TT serum levels were reduced below the
detection limit during docetaxel treatment (fT: from 0.37 pg/mL to <0.01
pg/mL and TT: from 0.12 to <0.05 ng/mL, respectively). Multivariate Cox
regression analyses identied fT nadir values <0.01 pg/mL, PSAR>50%,
number of organs involved and previous prednisone treatment as inde-
pendent prognostic risk factors for PFS and fT reduction >90%, number
of organs involved and previous prednisone as independent prognostic
risk factors for OS. FT nadir values <0.01 pg/mL and PSAR >50% were
associated with longer PFS (p<0.05).
Conclusions: ese data demonstrate that fT is an important prognostic
factor for PFS and OS in mPC patients.
Disclosure Statement: e authors declare no potential conicts of interest.
391
Advanced Renal Cell Carcinoma: First Results from the
Prospective Research Platform Carat for Patients with MRCC
in Germany
Peter J Goebell 1; Lothar Müller 2; Carsten Grüllich 3; Dietmar Reichert 4;
Martin Bögemann 5; Steen Dörfel 6; Eyck von der Heyde 7;
Adrian Binninger 8; Martina Jänicke 8; Norbert Marschner 9;
Michael Staehler 10; Viktor Grünwald 11
1Waldkrankenhaus St. Marien Urologische Universitätsklinik, Erlangen,
Deutschland
2Onkologie UnterEms Leer-Emden-Papenburg Dr. L. Müller, C. Janßen, Leer,
Deutschland
3Universitätsklinikum Carl Gustav Carus, Dresden, Deutschland
4Gemeinschaftspraxis für Hämatologie und Onkologie, Westerstede,
Deutschland
5Universitätsklinikum Münster (AöR), Münster, Deutschland
6Onkozentrum Dresden/Freiberg, Dresden, Deutschland
7Onkologische Schwerpunktpraxis, Hannover, Deutschland
8iOMEDICO, Freiburg, Deutschland
9Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg, Deutschland
10Klinikum der Universität München Campus Großhadern, München,
Deutschland
11Universitätsklinikum Essen, Essen, Deutschland
Purpose: e Tumor Registry Renal Cell Carcinoma (TNK) analyzed
treatment and outcome of patients (pts) treated in Germany from 2007-
17. CARAT is the successor registry, which continues to assess longitudi-
nal real world clinical outcome, incl. patient-reported outcomes (PROs)
and decentralized biobanking. Today, we introduce CARAT and report
on current changes of the treatment landscape in mRCC in Germany.
Methods: Since Dec 2017 150 pts have been enrolled in CARAT, expand-
ing the previous TNK (2007-17, 1500 pts). CARAT is an observational,
prospective, open, multicenter clinical research platform aiming to enroll
1000 pts by 150 sites. Pts with mRCC who start systemic 1stline treatment
are eligible. Treatment characteristics, clinical outcome and physician-re-
ported factors on treatment decision making are collected. Changes of the
treatment landscape are shown descriptively.
Results: By August 2019 >1700 pts with mRCC have been recruited. Me-
dian age is 68 years. 60% had intermediate risk (MSKCC) at start of 1st-
line. Median OS for pts with start of 1st-line 2007-17 is 19 months (>60%
events). If selected by trial eligibility criteria, the median OS is 27 months.
Pts who started treatment in 2018 mostly received pazopanib or sunitinib
(38%/34%). Since the approval (May 2018) 18% are treated with cabozan-
tinib. Preferred 2nd-line treatment changed from sorafenib/temsirolimus
(35%/21%, 2007-09), everolimus (33% 2010-12), everolimus/axitinib/
sunitinib (29%/19%/18%, 2013-15) to nivolumab (>60% since 2016). e
impact of new treatment options on OS will be analyzed.
Conclusions Pts in routine care in Germany are older and have inferior
prognosis than trial-eligible pts. CARAT complements results of RCTs
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with prospective data on clinical and PROs for pts with mRCC in routine
care. CARAT will show changes in the choice of treatment due to new
approvals, applied sequences and investigate the eectiveness in a “real
world” setting.
Disclosure Statement: None of the authors declare conicts of interests regarding
the topic of this abstract.
414
Early Mortality of Prostatectomy vs. Radiotherapy as a
Primary Treatment for Prostate Cancer: a Population-Based
Study from The United States and East Germany
Daniel Medenwald; Dirk Vordermark; Christian Dietzel
Universität Halle, Halle (Saale), Deutschland
Purpose: To assess the extent of early mortality and its temporal course
aer prostatectomy and radiotherapy in the general population.
Methods: Data from SEER-database and East German epidemiologic can-
cer registries were used for the years 2005-2013. Metastasized cases were
excluded.
Analysing overall mortality, year-specic Cox regression models were
used aer adjusting for age (including age squared), risk stage and grad-
ing. To estimate temporal hazards we computed year-specic conditional
hazards for surgery and radiotherapy aer propensity-score matching and
applied piecewise proportional hazard models.
Results: In German and US-American populations we observed higher
initial three-month mortality odds for prostatectomy (USA: 9.4, 95% CI:
7.8–11.2; Germany: 9.1, 95% CI: 5.1-16.2) approaching the null eect val-
ue not before 24 months (estimated annual mean 36 months in US data)
aer diagnosis.
During the observational period we observed a constant hazard ratio for
the 24-month mortality in the US-population (2005: 1.7, 95% CI: 1.5–1.9;
2013: 1.9, 95% CI: 1.6–2.2) comparing surgery and radiotherapy. e
same was true in the German cohort (2005: 1.4, 95% CI: 0.9–2.1; 2013:
3.3, 95% CI: 2.2–5.1). Considering low-risk cases, the adverse surgery ef-
fect appeared stronger.
Conclusions: ere is strong evidence from two independent populations
of a considerably higher early to midterm mortality aer prostatectomy
compared to radiotherapy extending the time of early mortality consid-
ered by previous studies up to 36 months (at least 24 months).
Disclosure Statement: All authors declare that there is no conict of interest.
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463
TKI Induction Followed by a Randomized Comparison
between Nivolumab or TKI Continuation in Renal Cell
Carcinoma (NiVOSWiTCH)
Viktor Grünwald 1; Carsten Grüllich 2; Philipp Ivanyi 3; Manfred Wirth 4;
Peter Staib 5; Martin Schostak 6; Philip Dargatz 7; Lothar Müller 8;
Michael Metz 9; Lothar Bergmann 10; Thomas Steiner 11; Manfred Welslau 12;
Anja Lorch 13; Philipp Schütt 14; Mohamed-Reza Rayan 15; Eva Hellmis 16;
Axel Hinke 17; Martin Mänz 18; Johannes Meiler 19; Thomas Kretz 20;
Wolfgang Loidl 21; Anne Flörcken 22
1Universitätsklinikum Essen , Klinik und Poliklinik für Urologie, Essen,
Deutschland
2Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland
3Medizinische Hochschule Hannover (MHH) Klinik für Hämatologie,
Hämostaseologie, Onkologie und Stammzelltransplantation, Hannover,
Deutschland
4Universitätsklinikum „Carl Gustav Carus“ der Technischen Universität Dresden,
Klinik und Poliklinik für Urologie, Dresden, Deutschland
5St.-Antonius-Hospital, Hämatologie/Onkologie, Eschweiler, Deutschland
6Universitätsklinikum Magdeburg, Klinik für Urologie, Magdeburg, Deutschland
7Johannes Wesling Klinikum Minden, Klinik für Hämatologie/Onkologie,
Minden, Deutschland
8Onkologie UnterEms Leer, Leer (Ostfriesland), Deutschland
9ConMed GmbH, Göttingen, Deutschland
10Universitätsklinikum Frankfurt, Medizinische Klinik II, Frankfurt am Main,
Deutschland
11Helios Klinikum Erfurt, Klinik für Urologie, Erfurt, Deutschland
12Onkologie Aschaenburg, Hämato-Onkologische Schwerpunktpraxis am
Klinikum Aschaenburg, Aschaenburg, Deutschland
13UniversitätSpital Zürich, Klinik für Medizinische Onkologie und Hämatologie,
Zürich, Schweiz
14Onkologische Schwerpunktpraxis, Gütersloh, Deutschland
15Krankenhaus Nordwest, Klinik für Onkologie und Hämatologie, Frankfurt am
Main, Deutschland
16Urologicum Duisburg, Duisburg, Deutschland
17CCRC Cancer Clinical Research Consulting, Düsseldorf, Deutschland
18AIO-Studien-gGmbH, Berlin, Deutschland
19Klinik Dr. Hancken GmbH, Stade, Deutschland
20Urologie Heinsberg, Heinsberg, Deutschland
21Ordensklinikum Linz Barmherzige Schwestern, Linz, Österreich
22Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt
Hämatologie, Onkologie und Tumorimmunologie, Berlin, Deutschland
Background: Treatment with tyrosine kinase inhibitors (TKI) or
Nivolumab (NIVO) are standard treatment options in metastatic renal cell
carcinoma (mRCC). We tested whether TKI with early switch to NIVO
improved outcome in mRCC.
Patients and methods: Key inclusion criteria: measurable advanced or
metastatic ccRCC, ECOG PS: 0-2, adequate organ function. Patients with
PR or SD to sunitinib or pazopanib aer 10-12 weeks of treatment were
1:1 randomized to continue TKI treatment or switch to NIVO 240 or 480
mg IV q2-4wks. Imaging was performed q12wks. 49 of 244 planned pa-
tients were randomized between December 2016 and August 2018 and
poor accrual led to premature closure of the trial. Ecacy and safety pa-
rameters were analyzed descriptively.
Results: 25 and 24 pts. received NIVO or TKI, respectively. Median age
was 65 years (range: 35-79), 40 pts. (82%) were male and 2 pts. (4%) had an
ECOG PS of 2. MSKCC risk categories were: favorable (31%), intermedi-
ate (65%), and poor (4%). Best objective response rate (ORR) from start of
1st line therapy was not signicantly dierent between groups (64 vs. 70%,
P=0.76). However, when measured from time of randomization ORR for
NIVO vs. TKI was 16 vs. 48% (P=0.029). All grades adverse events (AE)
occurred in 96% (NIVO) and 100% (TKI) and grade 3-5 were 44% vs.
67%, respectively. Serious AE (SAE) were 10 (40) and 9 (38), respectively.
Conclusions: Our results indicate that TKI-sensitive pts. have less ben-
et from early switch to NIVO treatment than from TKI continuation.
e major limitation of our trial is the premature closure and the limited
sample size.
Disclosure Statement: e authors declare no conict of interest.
Sponsor & funding source: AIO-Studien-gGmbH, nancial support: BMS
Clinical trial registry: Eudra-CT: 2016-002170-13. NCT02959554
488
Erdatinib Compared with Vinunine or Docetaxel or
Pembrolizumab in Patients (PTS) with Metastatic or Surgically
Unresectable (M/UR) Urothelial Carcinoma (UC) and Selected
FGFR Gene Alterations (FGFRALT): Phase 3 THOR Study
Florian Imkamp 1; Yohann Loriot 2; Andrea Necchi 3; Se Hoon Park 4;
Robert Huddart 5; Earle Burgess 6; Min Fu 7; Ademi Santiago-Walker 7;
Sutapa Mukhopadhyay 7; Vahid Naini 7; Kris Deprince 8; Manish Monga 7;
Arlene Siefker-Radtke 9
1Department of Urology, Hannover University Medical Center, Hannover,
Germany
2Institut Gustave Roussy, Villejuif, France
3Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
4Samsung Medical Center, Seoul, Korea
5Institute of Cancer Research, Sutton, London, UK
6Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North
Carolina, USA
7Janssen Research & Development, USA
8Janssen Research & Development, Beerse, Belgium
9University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
Purpose: Pts with M/UR UC have poor prognoses. Programmed death
(ligand)-1 (PD-[L]1) inhibitors have improved outcomes in some pts,
but responses vary based on genotypic subtype. FGFRalt are present in
20% of pts with UC and may reect an immunologically cold tumor that
does not respond well to immunotherapy.1 In early phase 2 study, erda-
tinib (ERDA, 8 mg/d continuous), a pan-FGFR (1-4) inhibitor demon-
strated tolerability and favorable objective response rate (ORR, 42%)
in pts with M/UR UC and FGFRalt; uptitration to 9 mg/d was feasible.
Activity of single-agent ERDA will be compared with chemo or pem-
brolizumab in pts with M/UR UC in this randomized phase 3 study.
Methods: Adult pts (ECOG status ≤ 2, adequate bone marrow, liver, and
renal function; no uncontrolled cardiovascular disease, known HIV, hepa-
titis B or C, or baseline phosphate persistently above upper limit of normal
allowed) with stage 4 M/UR UC and specic pathogenic FGFRalt (FGFR3
mutations or FGFR2/3 fusions), who have received 1 or 2 lines of prior
systemic therapy are eligible. Pts will be screened for FGFRalt and ran-
domized in 2 cohorts (1:1). Cohort 1 (n ~280): pts with prior chemo and
PD-L1 inhibitor (prior PD-[L]1 inhibitor -as monotherapy or combo; no
more than 2 lines of prior allowed for cisplatin-ineligible pts) in combi-
nation or in maintenance setting will receive 8 mg/d continuous ERDA
vs chemo (1:1) with docetaxel or vinunine. Cohort 2 (n ~350): pts with
prior chemo but no prior PD-(L)1 inhibitor will receive 8 mg/d ERDA
vs pembrolizumab (1:1). Uptitration of ERDA to 9 mg/d is recommend-
ed in pts with serum phosphate ≤ 9 mg/dL. Primary end point: overall
survival. Secondary end points: progression-free survival, ORR, duration
of response, pt-reported outcomes, safety, and pharmacokinetics. PD-L1
expression level per immunohistochemistry and UC subtype per RNA
sequencing or other methods as exploratory end points. Pts are being en-
rolled at sites in 25 countries. For additional information on specic sites/
countries refer clinicaltrials.gov (NCT03390504).
Reference:
1. Sieer-Radtke ASCO GU 2018
495
Activity of Two Routine Cabazitaxel Treatment Sequences
in Patients with Metastatic Castration- Resistant Prostate
Cancer (mCRPC) – Interim Analysis of The Non-Interventional
Scope Study
Carsten Bokemeyer 1; Burkhard Otremba 2; Richard Cathomas 3;
Franz Stoiber 4; Jürgen Gschwend 5
1Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
2Onkologische Praxis Oldenburg/ Delmenhorst, Oldenburg, Deutschland
3Kantonsspital Graubünden, Chur, Schweiz
4Salzkammergut Krankenhaus Vöcklabruck, Abt.für Urologie, Vöcklabruck ,
Österreich
5Klinikum rechts der Isar der Technischen Universität München, München,
Deutschland
Purpose: Cabazitaxel (CAB) and new hormonal therapies (HT: abi-
raterone or enzalutamide) have demonstrated a survival benet in the
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post-docetaxel setting. Optimal sequencing of these agents is unknown.
SCOPE is the rst multinational, non-interventional study evaluating
prospectively the activity of CAB according to dierent sequences.
Methods: SCOPE is aimed at recruiting 900 patients (pts.) starting treat-
ment with CAB in daily practice. Medical history, previous life-extending
therapies received and outcome during CAB therapy (PSA response, clin-
ical benet, pain relief, tumor response as per RECIST) are collected. Pts
are followed for up to 24 months aer start of CAB therapy. Treatment
outcomes (PSA, clinical including pain or radiological) are collected. For
the current interim analysis (cut-o FEB 04, 2019) preliminary treatment
outcomes of 2 sequences of therapies (DOC-CAB-HT and DOC-HT-
CAB) are provided. It is funded by Sano-Aventis Germany.
Results: Of 734 enrolled pts., 273 pts. currently completed CAB therapy
and are included in this interim analysis. 150 pts. (55%; med. age 70
yrs) received DOC-CAB-HT and 123 received DOC-HT-CAB (45%,
med. age 73 yrs). Of these 273 pts, 146 (53.5%) responded to CAB (DOC-
CAB-HT, n=87; DOC-HT-CAB, n=59), 76 (27.8%) had no response - out-
come was missing for 51 (18.7%). Responses to CAB (n=146) documented
were mainly a PSA decrease (≥30% or ≥50% in 92 or 63 pts, respectively)
, pain relief (n=18), clinical (n=36) and RECIST responses (n=13; PR n=6
; SD n=7). Med. PFS with CAB was 4.9 mo (95% CI 4.0-5.5) with DOC-
CAB-HT and 4.6 mo (95% CI 3.9-5.4) with DOC-HT-CAB (p=0.24). OS
data are not yet mature. TEAE were observed in 141 pts. (51.7%). Main
AE of CAB ≥ 5% were nausea (7.3%), fatigue (6.3%), anemia (5 %) and
diarrhea (4.7%).
Conclusions: Preliminary results of SCOPE prospective registry suggest
that under routine conditions, CAB is active (even aer new HT) and
shows manageable tolerability.
Reference:
1. Oncol Res Treat 20149;42(suppl 4):51. Published and presented Oktober 2019
by same authors
530
Anticancer Activity and Mechanism of Action of Derivatives
of The Marine Alkaloid Ascididemine in Drug-Resistant
Prostate Cancer
Moritz Kaune 1; Sergey A. Dyshlovoy 1, 2, 3, 4; Jessica Hauschild 1;
Tina Rohlng 1; Dmitry N. Pelageev 3; Valentin Stonik 3; Markus Graefen 4;
Carsten Bokemeyer 1; Gunhild von Amsberg 5, 6
1Department of Oncology, Hematology and Bone Marrow Transplantation with
Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center
Hamburg-Eppendorf, Hamburg, Deutschland
2Department of Organic Chemistry and Laboratory of Biologically Active
Compounds , School of Natural Sciences, Far Eastern Federal University ,
Vladivostok, Russland
3G.B. Elyakov Pacic Institute of Bioorganic Chemistry, Vladivostok, Russland
4Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf,
Hamburg, Deutschland
5Department of Oncology, Hematology and Bone Marrow Transplantation with
Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center
Hamburg-Eppendorf, Hamburg, Deutschland
6Martini-Klinik Prostate Cancer Center, University Medical Center Hamburg-
Eppendorf, Hamburg, Deutschland
Purpose: Marine organisms have served as a source for new potent anti-
cancer drugs. e marine natural compound Ascididemine, a pentacyclic
aromatic alkaloid, is known to exhibit antineoplastic activity.
Methods: Chemically optimized synthetic Ascididemine derivatives were
generated and screened for selective cytotoxicity against human prostate
cancer (PCa) cells. Most promising compounds were chosen for further
investigations in vitro. Eects on cell compartments, intracellular signal-
ing, proteome and kinome were investigated. Combinational treatment
with established and preclinical drugs were performed. Androgen-inde-
pendent, docetaxel-resistant PC3 cells and AR-V7 positive, BRCA2- mu-
tated 22Rv1 cells were investigated.
Results: Two out of 24 derivatives were identied to selectively and po-
tently inhibit drug-resistant PCa cells, while non-malignant cells were less
aected. e compounds induced a mitochondrial membrane- permea-
bilization followed by increase of reactive oxygen species levels and Ca2+
release by the endoplasmatic reticulum. Decreasing levels of intracellular
androgen receptor and its splice variant ARV7 were found. Kinome and
proteome analysis revealed a general upregulated kinomic activity, spe-
cically for the PI3K-Akt-pathway and PIM1 kinase. Coherently, combi-
nations with specic Akt inhibitors as well as PARP inhibitor Olaparib in
BRCA2-decient PCa cells revealed strong synergism. Moreover a syner-
gism in drug-resistant PCa cells was found for abiraterone, enzalutamide
and docetaxel, indicating a reconstitution of sensitivity to these anticancer
drugs.
Conclusions: We identied two potent marine-derived anticancer sub-
stances with high potential to overcome resistance mechanisms alone
and in combination with established drugs in PCa, thus lling a medical
demand. e mechanism of action includes the induction of mitochon-
drial damage leading to Ros generation and activation of endoplasmatic
reticulum stress with consequent caspase-dependent apoptosis. In vivo
examinations are ongoing.
546
Ecacy of Anti-PD(L)1 Treatment in Patients with Metastatic
Urothelial Cancer Based on mRNA- and Protein- Based PD-L1
Determination: Results from the Multicentric, Retrospective
Fosmic Trial
Jonas Jarczyk 1, 2; Ralph M. Wirtz 2, 3; Florian Roghmann 2, 4; Hendrik Jütte 2, 5;
Maximilian C. Kriegmair 1, 2; Thomas S. Worst 1, 2; Danijel Sikic 2, 6;
Sven Wach 2, 6; Helge Taubert 2, 6; Bernd Wullich 2, 6; Veronika Weyerer 2, 7;
Robert Stoehr 2, 7; Friedemann Zengerling 2, 8; Christian Bolenz 2, 8;
Johannes Breyer 2, 9; Maximilian Burger 2, 9; Stefan Porubsky 2, 10;
Arndt Hartmann 2, 7; Philipp Erben 1, 2; Markus Eckstein 2, 7
1Department of Urology, University Hospital Mannheim, University of
Heidelberg
2On behalf of the BRIDGE-Consortium e.V.
3STRATIFYER Molecular Pathology GmbH, Cologne
4Department of Urology, Marien-Hospital Herne, University Hospital Bochum,
University of Bochum
5Department of Pathology, University Hospital Bochum, University of Bochum
6Department of Urology and Pediatric Urology, University Hospital Erlangen,
University of Erlangen-Nuernberg
7Institute of Pathology, University Hospital Erlangen, University of Erlangen-
Nuernberg
8Department of Urology, University Hospital Ulm, University of Ulm
9Department of Urology, Caritas Hospital St. Josef, University of Regensburg
10Department of Pathology, University Hospital Mannheim, University of
Heidelberg
Purpose: Immunotherapy (IO) against PD1 or PD-L1 has been approved
for treatment of metastasized urothelial bladder cancer (mUC). Here we
evaluated ecacy in a retrospective Real-World-Phase IV trial based on
molecular subtypes and PD-L1 status.
Methods: Cancer specic survival (CSS) from start of IO treatment to
death was analyzed in a multicenter cohort of 65 patients having received
IO for mUC in 1st and 2nd line setting. Intrinsic molecular subtypes were
assessed by CK5, CK20, GATA3, FOXA1 and CD44 immunohistochem-
istry and RT-qPCR of CK5 and CK20. PD-L1 status was determined us-
ing the 28-8 Dako-assay. Stromal tumor inltrating lymphocytes were
assessed on HE slides. Survival analyses were performed by applying
clinically relevant cut-os and using Kaplan-Meier analysis and logistic
regression for CSS.
Results: Altogether, 43% of tumors presented with basal dierentiation,
57% were luminal. As expected, basal tumors exhibited signicantly high-
er levels of PD-1 and PD-L1 gene expression, higher amounts of sTILs and
PD-L1+ immune and tumor cells. Hierarchical clustering of all immuno-
logical biomarkers revealed three cluster: “Inamed high” (n=13, 20%),
“Inamed low” (n=22, 33.8%), and “Uninamed” (n=30, 46.2%). ere
were no signicant CSS dierences for any of these groups. However, pa-
tients with good performance status (ECOG0) and low PD-L1 expression
showed signicantly better CSS compared to those with ECOG0 / PD-L1
high and ECOG1 or ECOG2, respectively.
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Conclusions: Immunological determinants of mUC show comparable
distributions and correlations with subtypes of localized curatively treated
MIBC patients. Interestingly, data indicate improved CSS aer PD-1/PD-
L1 treatment in patients with good performance and low PD-L1 expres-
sion, which warrants validation in larger cohorts.
Disclosure Statement: Stratifyer carried out gene expression analysis, RW is
owner and employee of Stratifyer. Janssen Pharmaceutical gave research support
for this work. is abstract was submitted at Esmo 2019.
610
Prognostic Role of FGFR Mutations and FGFR mRNA
Expression in Metastatic Urothelial Cancer Treated with
Anti-PD(L1) Inhibitors in First an Second Line Setting
Florian Roghmann 1, 2; Ralph Wirtz 2, 3; Ademi Santiago-Walker 4;
Jonas Jarczyk 2, 5; Maximilian Kriegmair 2, 5; Thomas Worst 2, 5; Danijel
Sikic 2, 6; Sven Wach 2, 6; Helge Taubert 2, 6; Veronika Weyerer 2, 7; Robert
Stöhr 2, 7; Friedemann Zengerling 2, 8; Christian Bolenz 2, 8; Johannes Breyer 2, 9;
Maximilian Burger 2, 9; Stefan Porubsky 2, 10; Arndt Hartmann 2, 7;
Philipp Erben 2, 5; Markus Eckstein 2, 7; Hendrik Jütte 2, 11
1Department of Urology, Ruhr-University Bochum, Marien Hospital , Herne,
Deutschland
2on behalf of the BRIDGE-consortium e.V
3STRATIFYER Molecular Pathology GmbH, Cologne
4Janssen-Cilag GmbH, Deutschland
5Department of Urology, University Hospital Mannheim, Ruprecht-Karls-
University Heidelberg, Mannheim
6Department of Urology and Pediatric Urology, University Hospital Erlangen,
Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
7Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander
Universität Erlangen-Nürnberg, Erlangen
8Department of Urology, University Hospital Ulm, University of Ulm, Ulm
9Department of Urology, Caritas Hospital St. Josef, University of Regensburg,
Regensburg
10Department of Pathology, University Hospital Mannheim, Ruprecht-Karls-
University Heidelberg, Mannheim
11Department of Pathology, University Hospital Bochum, University of Bochum,
Bochum
Purpose: In the era of individualized oncological therapy in bladder can-
cer, FGFR3 mutations, FGFR2 and FGFR3 gene fusions as well as FGFR
mRNA expression as potential oncological targets and their association to
anti-PD-1 and anti-PD-L1 (IO) treatment outcomes in patients with met-
astatic urothelial cancer of the bladder (mUCB) was studied in a German
patient cohort.
Methods: Within a cohort of 72 patients with mUCB from 5 academic
centers in Germany (2016-2018) FGFR3 mutations, FGFR2 and FGFR3
gene fusions as well as FGFR expression in formalin-xed, paran em-
bedded tumour samples and its association to survival was examined
using SNaPshot PCR, RT-qPCR as well as Next Generation Sequencing.
Statistical analyses comprised Kaplan-Meier survival analyses, Spearman
rank correlations, non- parametric testing.
Results: In 17% of all patients, FGFR3 mutations or gene fusions could
be detected. Patients with FGFR3 alterations did not have better outcome
aer IO treatment (p=0.201). All alterations of FGFR3 resulted in overex-
pression of FGFR3 mRNA. Combination of FGFR mutation analysis and
FGFR mRNA assessment improved IO outcome prediction. Overexpres-
sion of FGFR3 mRNA was negatively associated with PDL1 expression
(mRNA and protein level). High FGFR2 mRNA expression in primary tu-
mors predicted better disease specic survival of mUCB patients receiving
IO therapy, whereas high FGFR3 mRNA expression was associated with
tumor specic death in patients exhibiting of low FGFR2 mRNA expres-
sions (p<0.05). is high risk group of mUCB patients exhibiting high
mRNA levels FGFR3 comprises 40% of the total cohort.
Conclusions: e assessment of FGFR mRNA by standardized RT-qPCR
identied a high risk mUCB patient cohort, which has inferior disease
specic survival despite IO treatment and overexpresses FGFR3 mRNA.
e assessment of FGFR mRNA levels by using this standardized, locally
applicable FGFR testing could identify an FGFR inhibitor target popula-
tion with poor response to IO treatment which is twice the size as current-
ly detected by FGFR genomic alterations alone.
619
Objectively Assessed Physical Activity and Sedentary
Behavior in Patients with Advanced Renal Cell Carcinoma
Christiane Hering-Schubert 1; Philipp Zimmer 2; Kathrin Schlüter 3;
Sybill Heßler 3; Valérie Perrot 4; Heiko Wunderlich 1
1St. Georg Klinikum Eisenach, Eisenach, Deutschland
2Deutsche Sporthochschule Köln, Köln, Deutschland
3IPSEN Pharma GmbH, Ettlingen, Deutschland
4IPSEN, Boulogne-Billancourt, Frankreich
Purpose: Increased levels of physical activity are associated with decreased
cancer risk and mortality in many cancer types. Moreover, physical ac-
tivity is known to reduce several side eects of cancer and its treatment
thereby improving patients’ quality of life (QoL). So far, most studies have
focused on frequently observed types of cancer, such as breast-, prostate-,
lung- and colorectal carcinoma. Recent data from epidemiological studies
also reported such relationships for renal cell carcinoma (RCC). Obser-
vational studies have included heterogenous populations in view of stage
of disease and treatment. Further, collected data on physical activity have
been based on self-reported assessments, a major limitation of these trials.
Methods: Against this backdrop we have initialized the multicenter ob-
servational CABOCARE trial in Germany and Austria. Patients with ad-
vanced RCC (n = 105) are recruited aer treatment decision for cabozan-
tinib has been made. Cabozantinib is an inhibitor of receptor tyrosine
kinases c-MET, VEGFR and AXL, which has proven to prolong progres-
sion free survival (PFS) compared to standard care with sunitinib. Patient
characteristics, state of disease, occurrence of adverse events (AE), quality
of life (FACT NFKSI-19), self-reported physical activity (newly developed
visual analogue scales) as well as objective physical activity, sedentary
behavior and sleep data (Actigraph® GT9X Link device) are recorded at
baseline, and each three months thereaer.
Results: Until data cut-o, baseline physical activity data were available
for three patients showing that the patients’ subjective and objective phys-
ical activity results were similar. e patients recorded predominately
light physical activity, and the mean time of moderate to vigorous physical
activity was below the recommended value of 150 minutes per week.
Conclusions: CABOCARE (NCT03647878) will be the rst observational
trial collecting objective physical activity and sleep data and their associ-
ations with PFS, AE and QoL in patients with advanced RCC in a longi-
tudinal fashion.
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2018
634
Dierent Diagnostic Methods for Identication of FGFR
Alteration in Advanced Urothelial Carcinomas: Prociency
ResultsBased on Multiple RNA Extraction Kits and Mutation
Detection Methods
Veronika Weyerer 1; Robert Stöhr 2; Hendrik Jütte 3; Ralph Wirtz 4;
Markus Eckstein 5; Florian Roghmann 6; Johannes Breyer 7; Stefan
Porubsky 8; Danijel Sikic 9; Christian Bolenz 10; Maximilian Kriegmair 11;
Arndt Hartmann 5; Philipp Erben 11
1Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander
University Erlangen-Nürnberg, Erlangen, Deutschland
2Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander
University Erlangen-Nürnberg
3Institute of Pathology, Ruhr University Bochum, Bochum, Deutschland
4STRATIFYER Molecular Pathology GmbH, Cologne, Deutschland
1Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander
University Erlangen-Nürnberg, Erlangen, Deutschland
6Department of Urology, Ruhr University Bochum, Bochum, Deutschland
7Department of Urology, University of Regensburg, Regensburg, Deutschland
8Institute of Pathology, Medical Faculty Mannheim, University of Heidelberg,
Mannheim, Deutschland
9Department of Urology and Pediatric Urology, , University Hospital Erlangen,
Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Deutschland
10Department of Urology, University of Ulm, Ulm, Deutschland
11Department of Urology, Medical Faculty Mannheim, University of Heidelberg,
Mannheim, Deutschland
Purpose: Pan FGFR inhibitors such as Erdatinib are approved in patients
with advanced urothelial carcinoma (aUC) harboring FGFR alterations.
Based on the necessity of sensitive and reproducible identication of these
alterations in diagnostic routines this study aimed to compare dierent
RNA isolation techniques and the QIAGEN therascreen® FGFR RGQ RT-
PCR Kit with the SNaPshot mutational analysis.
Methods: Nucleic acids were extracted from 47 UC patients using the
QIAGEN RNeasy DSP FFPE Kit, STRATIFYER Xtract or Maxwell RNA
(Promega) isolation kit. Mutations of the FGFR3 gene were detected using
the SNaPshot method as well as via the QIAGEN therascreen® FGFR RGQ
RT-PCR Kit. Intrinsic molecular subtypes were assessed using immuno-
histochemistry (IHC) of GATA3, FOXA1, CK20, CK5 and CD44 as well
as RT-qPCR for gene expression of CK20 and CK5.
Results: All three dierent RNA isolation kits showed comparable amount
of extracted RNA (Median 290, 177 and 226 ng/ul). Six hotspot FGFR3
mutations were identied with 100% concordance. e main dierence
were the necessary working hours: per 10 samples, 4 vs. 4.5 vs 8 hours
were needed for Stratifyer, Maxwell or QIAGEN RNA isolation. In addi-
tion, of 47 analyzed samples 100% concordance between QIAGEN ther-
ascreen® FGFR RGQ RT-PCR Kit and SNapShot analysis were achieved
with 18 mutations identied (14 S249C, 2 R248C and 2 Y375). Immuno-
histochemical basal marker prole (CD44 and CK5) as well as high CK5
expression was observed in 28 (6/28 FGFR3-altered). Luminal marker
prole (IHC markers: GATA3, FOXA1 and CK20 as well as expression
of CK20) was detected in 37 samples (5/37 with FGFR3 alteration, n.s.).
Conclusions: Dierent RNA extraction methods presented with compa-
rable amount of nucleic acids with variant working hours. Moreover, a
100% concordance between the well established SNaPshot analysis com-
pared to the QIAGEN therascreen® FGFR RGQ RT-PCR Kit for FGFR3
mutations was observed. So far, the frequency of FGFR3 mutations in aUC
was not related to the type of UC as dened by marker proles.
676
Central, Prospective Detection of Homologous Recombination
Repair (HRR) Gene Alteration in Tumor Tissue From> 4000
Men with Metastatic Castration-Resistant Prostate Cancer
(mCRPC) Screened for The Profound Study
A Stenzl 1; M Hussain 2; K Fizazi 3; F Saad 4; N Shore 5; S Sandhu 6; N Mehra 7;
MKolinsky 8; G Roubaud 9; M özgüroğlu 10; N Matsubara 11; C Gedye 12;
Yd Choi 13; C Padua 14; C Goessl 15; A Kohlmann 16; C Corcoran 16;
CaAdelman 16; AAllen 15; J Burgents 17; J de Bono 18
1Department of Urology, Eberhard-Karls-University, Tübingen, Deutschland
2Robert H Lurie Comprehensive Cancer Center, Northwestern University
Feinberg School of Medicine, Chicago, United States
3Institut Gustave Roussy, University of Paris Sud, Villejuif, Frankreich
4Centre Hospitalier de l’Université de Montréal/CRCHUM, Montreal, Kanada
5Carolina Urologic Research Center, Myrtle Beach, United States
6Peter MacCallum Cancer Centre, Melbourne, Australien
7Radboud University Medical Center, Nijmegen, Niederlande
8University of Alberta Cross Cancer Institute, Edmonton, Kanada
9Institut Bergonié, Bordeaux, Frankreich
10Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul,
Turkey
11National Cancer Center Hospital East, Chiba, Japan
12Calvary Mater Newcastle, Waratah, Australien
13Yonsei University College of Medicine, Seoul, Südkorea
14Cetus Medicina Oncológica, Betim, Brasilien
15AstraZeneca, Gaithersburg, United States
16AstraZeneca, Cambridge, United Kingdom
17Merck & Co, Inc, Kenilworth, United States
18The Institute of Cancer Research and Royal Marsden, London, United Kingdom
Purpose: A proportion of patients (pts) with mCRPC have tumor cells
harboring HRR gene alterations that may confer sensitivity to PARP inhi-
bition. e PROfound study (NCT02987543) is a phase III, randomized,
multicenter trial evaluating the ecacy and safety of the PARP inhibitor
olaparib versus physicians choice of enzalutamide or abiraterone acetate
in pre-treated mCRPC pts with a qualifying alteration in 15 predened
genes with a direct or indirect role in HRR. Here, we report the prevalence
of single and co-occurring HRR alterations in pts screened for PROfound.
Methods: An investigational next-generation sequencing assay developed
in partnership with Foundation Medicine Inc. (FMI) was used to
prospectively select patients harboring HRR gene alterations in their
tumor tissue reporting deleterious or suspected deleterious qualifying
alterations in 15 HRR genes. Samples were clinically heterogenous
regarding location and timing. Pts with a qualifying alteration who met
the eligibility requirements were randomized to the trial. e study
comprised two cohorts; Cohort A: pts with alterations in BRCA1, BRCA2
or ATM (assigned regardless of any co-occurring mutation in other
genes); Cohort B: 12 other HRR genes.
Results: Of 4425 screened pts, 4047 had samples tested at FMI, of whom
2792 (69%) yielded a biomarker status result. A qualifying HRR alteration
was detected in 778 (27.9%) pts. Among the Cohort A genes, alterations
in BRCA2 were the most common (9.7%) followed by ATM (6.3%) and
BRCA1 (1.3%). CDK12 alterations (7.1%) were the most common among
the other HRR genes. A co-occurring qualifying HRR alteration in more
than 1 gene was detected in 59 (7.6%) patients, most commonly BRCA2
(n=30), CDK12 (n=24) or ATM (n=13).
Conclusions: is is the largest study to date with central prospective
HRR gene alteration tissue testing in prostate cancer. HRR alterations
were most common in BRCA2; followed by CDK12 and ATM. Further
analyses are warranted to help understand whether there is a correlation
between clinical/demographic characteristics and HRR alterations.
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2018
720
Role of Free Testosterone Serum Levels During Salvage
Chemotherapy with Carboplatin Plus Weekly Docetaxel in
Patients with Docetaxel-Refractory, Metastatic Castration-
Resistant Prostate Cancer (mCRPC)
Stefan Brunotte 1; Paula Kappler 1; Philipp Ivanyi 1; Michael Morgan 2;
Christoph von Klot 3; Christoph Reuter 1
1Hämatologie, Hämostaseologie, Onkologie, Stammzelltransplantation,
Medizinische Hochschule Hannover, Hannover, Deutschland
2Experimentelle Hämatologie, Medizinische Hochschule Hannover, Hannover,
Deutschland
3Urologie & Urologische Onkologie, Medizinische Hochschule Hannover,
Hannover
Purpose: Carboplatin plus docetaxel (CD) may be eective in mDRPC.
Platinum(II)-complexes interfere with steroid biosynthesis lowering tes-
tosterone levels. In this study, the impact of CD on free and total testos-
terone (fT, TT) serum levels and the prognostic role of fT and TT were
analyzed in mPC patients.
Methods: Docetaxel failure/resistance was dened according to the Pros-
tate Cancer Working Group (PCWG2 2007) criteria. Treatment consisted
of at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 every 4
weeks (q4w), docetaxel (35 mg/m2) iv for one hour on days 1, 8, (15)
plus prednisone 2x5mg/day orally aer receiving informed consent until
disease progression or occurrence of intolerable adverse eects. Ecacy
measures were done following PCWG2 recommendations.
Results: Of the 118 pts. treated since February 2005, 95.8% had bone,
47.5% lymph node, 28.0% liver and 20.3% lung metastases. At the time
of the current analysis, the median follow-up time was 14.4 months. e
objective response rate (ORR) was 46.4% in the 69 pts. with measureable
disease (58.5%). Response of prostate-specic antigen (PSAR ≥ 50%) was
observed in 56 (47.9%) patients. Median progression free survival (PFS)
was 7.6 months (CI 95% 6.0, 9.1) and median overall survival (OS) was
15.7 months (CI 95% 12.2, 19.2). e most common reversible grade 3/4
toxicity was leukopenia/ neutropenia (36.4/28.8%). Median FT serum
levels were 0.35 pg/mL before and < 0.18 pg/mL during CD treatment
(nadir levels, p < 0.001; detection limit < 0.18 pg/mL). In multivariate
analyses, LDH>2xULN, PSAR≥50% and FT nadir levels below the
detection limit (< 0.18 pg/mL) during CD treatment were associated with
longer PFS (p < 0.05).
Conclusions: ese data suggest that CD may be an important salvage
treatment option for DRPC patients by inhibition of the testosterone bio-
synthesis.
Disclosure Statement: e authors declare no potential conicts of interest.
727
A Phase 3, Randomized, Open-Label, Multicenter,
Global Study of Ecacy and Safety of Durvalumab in
Combinationwith Gemcitabine+CiSPLATiN (G+C) for
Neoadjuvant Treatment Followed By Durvalumab Alone for
Adjuvant Treatment in Muscle-Invasive Bladder Cancer (MiBC)
(NiAGARA)
Hubert Rudolf Kübler 1; Thomas Powles 2; Joshua J Meeks 3;
MatthewGalsky 4; Michel S. van der Heijden 5; Hiroyuki Nishiyama 6;
HikmatAl-Ahmadie 7; Ashok Gupta 8; Jiabu Ye 9; Sarah Donegan 10;
DanaGhiorghiu 11; Salvatore Ferro 12; James Catto 13
1Uniklinikum Würzburg, Klinik und Poliklinik für Urologie und Kinderurologie,
Würzburg, Deutschland
2Queen Mary University of London, Barts Cancer Institute, London, United
Kingdom
3Northwestern University, Northwestern Medicine, Chicago Illinois , United
States
4The Mount Sinai Hospital, Hematology and Oncology faculty, New York,
United States
5Netherlands Cancer Institute, Molecular Carcinogenesis Division, Amsterdam,
Niederlande
6University of Tsukuba , Department of Urology, Ibaraki , Japan
7Memorian Sloan Kettering Cancer center, The David Solit Lab, New York ,
United States
8Astrazeneca, Immuno-Oncology , Gaithersburg, United States
9Astrazeneca, Biostatistic , Washington DC, United States
10Astrazeneca, Medical Scientist Immuno-Oncology, Washington DC, United
States
11Astrazeneca, Global Clinical Lead, Cambridge, United Kingdom
12Astrazeneca, Global Study, Gaithersburg, United States
13The University of Sheeld , Department of Oncology & Metabolism, Sheeld,
United Kingdom
Purpose: In the management of MIBC, neoadjuvant cisplatin-based com-
bination chemotherapy has demonstrated improved pathologic complete
response (pCR), event-free survival (EFS), and OS compared with rad-
ical cystectomy alone. Many patients still develop recurrence, including
progression to metastasis. e combination of chemotherapy and immu-
notherapy in a neoadjuvant setting and consolidating response post-cys-
tectomy in the adjuvant setting may improve clinical outcomes. PD-L1
inhibition with durvalumab, in combination with a standard neoadjuvant
regimen (G+C), may improve immune-mediated antitumor response and
increase the rates of pathologic responses and long-term survival.
Methods: NIAGARA is a Phase 3, randomized, open-label, multicenter,
global study (~1050 patients) with 1:1 randomization to durvalumab and
G+C combination (Arm 1) or G+C (Arm 2) as neoadjuvant chemother-
apy prior to radical cystectomy. Following radical cystectomy and during
adjuvant therapy, patients in Arm 1 will receive durvalumab monother-
apy for 8 cycles; patients in Arm 2 will receive no adjuvant treatment.
Patients with resectable MIBC (clinical stage T2N0M0-T4aN0M0) with
transitional cell histology planning to undergo a radical cystectomy will
be included. Primary endpoints are pCR rates at time of cystectomy fol-
lowing neoadjuvant treatment and EFS. Secondary and exploratory end-
points include proportion of patients who achieve pathologic response
<P2 (stages Pa, P1, and CIS) at time of cystectomy following neoadjuvant
treatment, EFS at 24 months, metastasis-free survival, proportion of pa-
tients who undergo cystectomy, and OS at 5 years. Enrollment opened in
Dec 2018.Clinical trial information: NCT03732677.
Results: Not yet available.
Conclusions: Not yet available.
References:
1. Iyer G and Rosenberg JE. Ann Oncol. 2018;29:2302-2312.
2. Abufaraj M, et al. Transl Androl Urol. 2016;5:735-744.
3. Dimitriadis I and Bamiais A. Eur Oncol Haematol. 2017;13:134-138.1
Disclosure Statement: Funded by AstraZeneca.
DE-21760/19
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2018
787
Comparison of Online Information About Prostatectomy,
Radiotherapy and High-Intensity Focused Ultrasound for
Prostate Cancer Patients
Alexander Rühle 1; Thorben Hölscher 2; Lukas Käsmann 3
1University Hospital Freiburg, Department of Radiation Oncology, Freiburg,
Deutschland
2University Cologne, Faculty of Medicine, Deutschland
3University Hospital, LMU Munich, Department of Radiation Oncology,
Deutschland
Purpose: While the importance of the Internet as information source for
prostate cancer patients is increasing, there is little knowledge about the
relation between the prostate cancer treatment modality and the websites
quality, readability and popularity.
Methods: By using the search engine Google, an Internet search for the
English terms “prostate cancer prostatectomy”, “prostate cancer radiother-
apy” and “prostate cancer hifu” as well as for the corresponding German
terms “Prostatakrebs Prostatektomie, “Prostatakrebs Strahlentherapie
and “Prostatakrebs HIFU” was conducted. e websites quality of the
rst 30 search results was assessed by validated instruments such as the
DISCERN Plus score, the JAMA benchmark criteria and the Health on
the Net Code of Conduct (HONcode) certication. e readability of the
websites was analyzed with the Flesch-Reading-Ease, and the average us-
age time was assessed using Alexa Internet.
Results: Regarding the DISCERN Plus instrument and JAMA benchmark
criteria, the websites quality was moderate with no dierences between
English and German websites. Using the JAMA benchmark criteria, the
quality of German radiotherapy websites was signicantly increased com-
pared to German HIFU websites. Similarly, there were signicantly more
websites with HONcode certication in the German radiotherapy group
than in the HIFU group; however, the majority of websites exhibited no
HONcode certication. Based on the Flesch-Reading-Ease, both English
and German websites were dicult to read with no dierences between
the surgery, radiotherapy and HIFU group. Likewise, the average user
time did not dier among the groups.
Conclusions: As the overall quality of the investigated websites is mod-
erate, the internet may be helpful in the treatment decision process of
prostate cancer patients. However, regarding the insucient readability
of many websites, a signicant number of patients have diculties to ob-
tain the relevant information highlighting the importance of high-quality
medical consultations by physicians.
832
A Prospective Phase 2A Study of Focal HDR Brachytherapy
for Low to Intermediate Prostate Cancer - Profocal
Peter Hass 1; Frank Fischbach 2; Daniel Schindele 3; Katharina Fischbach 4;
Martin Schostak 3; Maciej Pech 2; Thomas Brunner 5
1University Hospitals Magdeburg, Dept. of Radiation Oncology, Deutschland
2University Hospitals Magdeburg, Department of Diagnostic and Interventional
Radiology, Magdeburg, Deutschland
3University Hospitals Magdeburg, Department of Urology, Magdeburg,
Deutschland
2University Hospitals Magdeburg, Department of Diagnostic and Interventional
Radiology, Magdeburg, Deutschland
5University Hospitals Magdeburg, Dept. of Radiation Oncology, Magdeburg,
Deutschland
Purpose: An interim report on the feasibility of the technique and results
on tolerability and PSA course.
Methods: Single fraction interstitial HDR brachytherapy was performed
in patients with biopsy proven low to intermediate risk prostate cancer
(PC) of 1 lesion with an encompassing dose of ≥20Gy. Catheters were
placed into the lesions in a 3T-MRI system in local anesthesia. Follow up
was planned for PSA levels aer 3, 6, 12 and 24 months, a multiparamet-
ric (mp) MRI examination aer 6, 12 and 24 months and a re-biopsy 12
months aer HDR brachytherapy.
Results: e rst 9 patients with a follow-up for 6 months had tumors
exclusively located in the anterior part of the prostate mostly in the apical
region. Overall procedure time was 52 min and actual intervention time
34 min for the placement of the catheters. Median time of radiotherapy
was 8.3 min. Median encompassing dose was 27.4 Gy, median dose to
2 mL of rectum and bladder were 4.9 Gy and 8.5 Gy respectively. Using
the VAS scale the pain reported for the intervention ranged from 2 to 3.
No other complications were reported except for mild hematuria the day
aer the procedure in one patient. Short term follow up of at least six
months demonstrated no acute genitourinary or gastrointestinal toxicity.
Despite of the absence of antibiotic prophylaxis none of the patients
developed post-interventional signs of infection. PSA levels in all patients
decreased signicantly (from 8,9 to 1,7ng/ml on average). No residual or
recurrent prostate carcinoma was imaged at follow-up multi-parametric
MRI. Imaging results were conrmed by transrectal ultrasound (TRUS)
guided biopsies (n=4/9) showing no residual or recurrent prostate
carcinoma in the treated region at 12 months aer therapy.
Conclusions: HDR brachytherapy for localized PC is feasible and safe.
Catheters can be placed accurately and maximum therapeutic dose distri-
bution can be restricted to the tumour, no general anesthesia or antibiosis
is necessary.
851
Surgical Treatment of Synchronous and Metachronous
Metastatic Adrenal Tumors in Patients with Renal Cell
Carcinoma
Avetik Muradyan; Andrey Kostin; Nikolai Vorobyev; Hewad Taraki;
Aleksander Tolkachev
P. A. Hertsen Moscow Oncology Research Center - branch of FSBI NMRRC of
the Ministry of Health of Russia, Urological oncology department, Moscow,
Russland
Purpose: A comparative analysis of surgical treatment results in patients
with synchronous and metachronous solitary metastatic adrenal tumors
renal cell carcinoma origin.
Methods: Between 1997 and 2018, 93 patients (66 men and 27 women;
median age 60 years (28-78)) underwent surgical treatment, 58 patients
underwent simultaneous surgery for synchronous metastasis in the ad-
renal gland, and 35 patients underwent adrenalectomy due to a solitary
metachronous lesion.
Results: e sensitivity of ultrasound in the diagnosis of adrenal tumors is
80.6%, and computed tomography - 93.5%. Adrenal biopsy was successful
in 73.9%. Progression free survival (adrenal metastasis) aer the previous
primary surgical treatment was 44 months (5-204). During surgical treat-
ment of metachronous metastases, a decrease in the volume of blood loss
(p = 0.006), the average length of stay (p <0.0001), and the frequency of
postoperative complications (p = 0.022) were observed. During pathology
report study, clear cell RCC was observed in 84.9% (n = 79), papillary in
9.7% (n = 9), chromophobe in 2.2% (n = 2), and Collecting duct carcino-
ma (Bellini) in 3.2 % (n = 3).
e median follow up time was 42.0 ± 13.4 months (in the synchronous
lesion group - 24.0 ± 5.4 months, the median in the metachronous lesion
group was not achieved). e one-year survival of patients with a meta-
chronous lesion of adrenal was 82.3 ± 76.6% versus 52.8 ± 7.1% in the
synchronous lesion group, three-year survival was 79.2 ± 7.0% versus 32.3
± 7.6% and ve-year - 57.0 ± 10.0% versus 16.2 ± 12.0%. Metachronous
adrenal lesion (p <0.0001) and time to metastasis ≥24 months (p = 0.007)
were favorable prognosis factors. In a multivariate analysis, only a meta-
chronous lesion aected survival (p = 0.002).
Conclusions: Performing adrenalectomy among patients with a solitary
metachronous lesion can improve OS and PFS.
Disclosure Statement: no conict of interest
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2018
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2018
Geriatric Oncology
Poster
369
Changes in Survival Rates and Tumor Characteristics with
Increasing Age: Results from Population-Based Cancer
Registries
Klaus Kraywinkel 1; Birgitt van Oorschot 2; Julia Fiebig 1; Ulrich Wedding 3
1Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland
2Universitätsklinikum Würzburg, Interdisziplinäres Zentrum für Palliativmedizin
an der Klinik und Poliklinik für Strahlentherapie, Würzburg, Deutschland
3Universitätsklinikum Jena, Abteilung für Palliativmedizin, Jena
Purpose: A high proportion of cancers aect individuals of older age, for
whom guidelines are applicable only to a limited extent due to comorbid-
ities or other factors. It has frequently been shown that cancer survival
rates are considerably lower for patients aged 75 and older, even when
taking age related life expectancy into account (relative survival). Still,
little is known about how these results evolve with advancing age and if
they correspond to changes in tumor characteristics. We therefore investi-
gated how relative survival rates, distribution of tumor stage and grading
change with advancing age for selected common cancers. In addition, we
examined the use of adjuvant chemotherapy in stage III colorectal cancer
according to age and sex.
Methods: Analyses were based on data from German population-based
cancer registries for the period 2012–2016, including patients aged 60
years or older with cancer of the bowel, bladder, lung, stomach, prostate
or breast as well as mature B-cell neoplasms. All results were calculated by
tumor site, sex and 5-year age groups (60-64 to 90+ years).
Results: Although the relative survival rates for all investigated entities
decreased continuously, particularly in the age groups from 65–69 to 85–
89 years, the results were inconsistent in terms the distribution of tumor
stages and grading: invasive bladder cancer showed a trend toward earlier
stages with increasing age, while the proportion of poorly dierentiated
tumors in gastric and lung cancer decreased. e proportion of adjuvant
chemotherapies for colorectal cancer with lymph node involvement re-
corded in the registries declined signicantly, particularly aer the age
of 75.
Conclusion Overall, the drop in relative survival rates with advancing age
cannot be explained by changes in tumor characteristics alone. Less ag-
gressive treatment strategies due to a higher prevalence of comorbidities,
dierent patient preferences and lower degrees of scientic evidence are
likely to have an inuence on these results.
Disclosure Statement: No conlict of interest
503
TrainIng Programs Promoting Daily Activity and Physical
Function of Older Patients with Cancer – a Questionnaire
Based Survey Regarding Individual Needs and Preferences
Stephanie Witte 1; Daniel Medenwald 2; Andre Golla 3; Eni Shehu 1;
DirkVordermark 2; Patrick Michl 4; Masha Binder 5; Joern Ruessel 6;
AnkeSteckelberg 1; Heike Schmidt 1
1UKH Institut für Gesundheits- und Pegewissenschaft, Halle (Saale),
Deutschland
2Universitätsklinikum Halle Universitätsklinik und Poliklinik für Strahlentherapie,
Halle (Saale), Deutschland
3Institut für Rahabilitationsmedizin , Halle (Saale), Deutschland
4UKH Universitätsklinik und Poliklinik für Innere Medizin I, Halle (Saale),
Deutschland
5UKH Universitätsklinik und Poliklinik für Innere Medizin IV, Halle (Saale),
Deutschland
6Carl-von-Basedow-Klinikum Saalekreis Medizinische Klinik II, Merseburg,
Deutschland
Purpose: Physical function of older patients with cancer oen decreases
during cancer therapy. is study aims to explore individual needs and
preferences of older patients with cancer in order to promote their phys-
ical activity (PA.)
Methods: e study is designed as a multi-center questionnaire-based
survey including a convenience sample of patients aged ≥ 60; ≥70 and
≥80 years with heterogeneous cancer diagnoses and stages; either receiv-
ing therapy or aer care. e questionnaire covers: gender; age; diagnosis
and life situation; previous and recent PA; changes of PA due to the cancer
diagnosis; individual goals for exercising; preferred type of PA; preferred
physical and social environment for exercising (e.g. individual training vs.
group based; home based vs. sport-center); aspects of motivation; need
for support; self-ecacy and the use of digital media. Data are analyzed
descriptively.
Results: In four centers 64 patients with a mean age of 69 ± 6.4 years; n=34
male; participated. e main cancer sites were hematological (n=17); lung
(n=9); breast (n=8) and pancreas (n=7). Patients stated their interest in
exercising to improve their mobility and physical performance (n=38) to
prevent falls (n=26); to relax (n=15) and reduce fatigue (n=14). Patients
preferred outdoors activities e.g. walking (n=48); cycling (n=38) and
gymnastics either at home (n=36); in a group (n=26) or with a partner
providing motivational support (n=23). For independent exercises at
home; personalized recommendations and instructions (paper-based
or video-based) were considered helpful (n=40). Digital media are used
regularly (n=31) or sometime by (n=12) patients.
Conclusions: e study provides useful insights into preferences; needs
and motivational factors for PA in older patients with cancer. Digital me-
dia seem to be feasible to reach this target group.To improve representa-
tiveness; the survey is currently expanded to n=280 participants including
three more oncological centres.
Disclosure Statement: e authors do not have any conicts of interest relevant to
the topic to declare.
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2018
599
Development of a Multimodal Supportive Intervention to
Promote Physical Functioning of Older Patients with Cancer
Eni Shehu 1; Sigrid Roggendorf 1; André Golla 2; Gundula Hübner 3;
GabrieleStangl 4; Andreas Lau 5; Andrea Diestelhorst 6; Dirk Vordermark 6;
Anke Steckelberg 1; Heike Schmidt 1, 6
1Institut für Gesundheits- und Pegewissenschaft, Medizinische Fakultät der
Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland
2Institut für Rehabilitationsmedizin, Medizinische Fakultät der Martin-Luther-
Universität Halle-Wittenberg, Halle (Saale), Deutschland
3Institut für Psychologie, Martin-Luther-Universität Halle-Wittenberg, Halle
(Saale), Deutschland
4Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität
Halle-Wittenberg, Halle (Saale), Deutschland
5Institut für Sportwissenschaft, Martin-Luther-Universität Halle-Wittenberg,
Halle (Saale), Deutschland
6Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Halle (Saale),
Halle (Saale), Deutschland
Purpose: Physical function (PF) of older patients with cancer may decline
during therapy and endanger selfcare, independence and health related
quality of life (HRQOL). To prevent deterioration of PF and maintain
independence, targeted strategies considering the heterogeneity of older
people are needed. is study aims to develop and evaluate a multimod-
al supportive intervention to maintain PF and nutritional status of older
cancer patients undergoing outpatient radiotherapy.
Methods: e approach is based on the UK MRC Framework for the
development and evaluation of complex interventions involving clinical
experts and cancer survivors aged >60 years in development and pretest.
Assessments: comprehensive geriatric assessment, objective and subjec-
tive assessments of PF, nutrition, HRQOL, specic needs, goals, individ-
ual barriers and facilitators. Subsequent pilot-testing will be accessible
via digital media or paper based to examine which mode results in better
motivation and adherence.
Results: Each patient will receive tailored exercise and nutritional recom-
mendations according to his/her baseline assessments’ results. Pretest in-
cluding exercising and focus group interviews indicates feasibility and po-
tential usefulness of the exercises for maintaining everyday-functionality.
Participants appreciated the exibility of the programme, which includes
exercises in sitting and standing position. ey reported having stopped
rehabilitation classes since these were too strenuous. ey valued coor-
dination and balance exercises for increasing condence and preventing
falls. Participants rated their relatives’ help as a cornerstone for overcom-
ing their weaker self.
Conclusions: ere is a need in this target group for individually tailored
exercises that can be implemented in everyday life. e home-based inter-
vention comprises feasible exercises relevant for everyday functioning ad-
dressing endurance, coordination, balance and ne motor skills in sitting
or standing positions and nutritive advice.
Disclosure Statement: No conicts of interest
612
Social Relations of Older Patients with Cancer - Development
During the Disease Trajectory. A Retrospective, Qualitative
Study
Sigrid Roggendorf 1; Sven Weise 2; Patrick Michl 3; Dirk Vordermark 4;
OliverArránz Becker 5; Anke Steckelberg 1; Heike Schmidt 1, 4
1Institut für Gesundheits- und Pegewissenschaft, Medizinische Fakultät der
Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland
2Sachsen-Anhaltische Krebsgesellschaft e.V., Halle (Saale), Deutschland
3Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Innere
Medizin I, Medizinische Fakultät der Martin-Luther-Universität
Halle-Wittenberg, Halle (Saale), Deutschland
4Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für
Strahlentherapie, Medizinische Fakultät der Martin-Luther-Universität
Halle-Wittenberg, Halle (Saale), Deutschland
5Institut für Soziologie, Martin-Luther-Universität Halle-Wittenberg, Halle
(Saale), Deutschland
Purpose: Social support is a domain of the geriatric assessment. However,
little is known about the development of social relationships during the
course of the disease, especially among older people with cancer. e aim
of this study was to explore the experiences of older patients with cancer
regarding the development of their social relationships during disease
trajectory.
Methods: A qualitative retrospective approach was chosen. People with
cancer aged ≥65 years at diagnosis, at least 6 months aer treatment were
interviewed using a semi-structured interview guide and asked to depict
their social relations at four given time points using the Family Board a
non-verbal method to visualize social relations. e audiotaped interviews
were transcribed, the Family Board constellations were documented and
qualitative content analysis was conducted. Ethical approval was obtained.
Results: Six women and four men (mean age: 74.5 years) participated. e
tumor sites were prostate, gastric, pancreas, esophagus, lymphatic glands,
and brain. Analyses revealed that all participants experienced changes in
their social network. Disease-related reduction of physical function was
experienced to lead to the loss of social and role function. Grandchildren
were perceived as supporting the ghting spirit and the return to every-
day life. Comparisons of the Family Board constellations showed growing
closeness of familial relations especially during treatment which remained
later on. Frequent changes in number, closeness or distance related to oth-
er non-family ties. Participants valued these ties as another important
source of emotional and instrumental support.
Conclusions: Findings underline the importance of repeated assessments
of social relations and the availability of social support. e Family Board
was well accepted and provided useful additional information especially
regarding the perceived development of social relations.
Disclosure Statement: No conicts of interest.
618
Supportive Needs and Burden of Older Patients with Cancer
and their Spouses- a Qualitative Analysis of Semi-Structured
Interviews
Marlene Dieke 1, 2; Anke Steckelberg 2; Patrick Michl 3; Dirk Vordermark 4;
Heike Schmidt 2, 4
1Universitätsklinik und Poliklinik für Pädiatrie II, Universitätsklinikum Halle
(Saale), Halle (Saale), Deutschland
2Institut für Gesundheits-und Pegewissenschaft, Medizinische Fakultät der
Martin-Luther Universität Halle-Wittenberg, Halle, Deutschland
3Universitätsklinik und Poliklinik für Innere Medizin I, Universitätsklinikum Halle
(Saale), Halle (Saale), Deutschland
4Universitätsklinik und Poliklinik für Strahlentherapie, Universitätsklinikum
Halle (Saale), Halle (Saale), Deutschland
Purpose: Cancer and cancer therapy may cause burden of illness for pa-
tients and spouses likewise. is study aimed to explore needs and burden
of older cancer patients and their spouses during the disease trajectory.
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Methods: Within a qualitative retrospective design with semi-structured
interviews experiences of patients and their partners were explored. Pa-
tients 65 years and older having completed therapy and their partners
(dyads) were eligible. e interview transcripts were analyzed according
to qualitative content analysis (Mayring).
Results: Nine dyads were included. Mean age of patients was 74 years, of
partners 73 years, main tumor sites were: prostate (n=4), gastrointestinal
(n=3), breast (n=2). Patients were treated with: operation (n=10), chemo-
therapy (n=4) and radiotherapy (n=6), the most frequent comorbidity was
hypertension (n=9). Data analysis revealed positive and negative experi-
ences regarding 6 main themes: 1. Information of patients and partners
about illness and treatment: “My husband is still grateful. e doctor took
his time to explain everything.” 2. Empathic communication: “Tell your
wife: Sex is over, 3. Trans-sectoral care: “I got discharged and did not
know what to do, 4. Burden of illness regarding symptoms, side eects or
late eects (e.g. fatigue, impotence, incontinence): “Everything is dierent
than before, I got weaker, 5. Eects of illness and therapy on partnership
and sexuality including emotional burden and supportive needs of part-
ners: “it was not easy, I missed it (sexuality), there was a big gap, 6. Dyadic
coping: “my wife always backed me, she endured more than I can think
of, “I worry about him (partner with cancer), but I do not talk about my
feelings because I do not want to burden him.
Conclusions: e importance of empathic communication, information,
participation in decision making, the need for support regarding dyadic
coping and issues of intimacy and sexuality became evident. Due to the
qualitative design, these ndings should be examined in further studies.
Disclosure Statement: No conicts of interest
706
Meaningfulness of a Biological Marker (Advanced Glycation
Endproducts) Measured By Noninvasive Skin-Scan
(Autouorescence Measurement) in Geriatric-Oncological
Patients
Johannes Horn 1; Gabriele Meyer 2; Heike Schmidt 2; Franziska Flessner 2, 3;
Andreas Simm 4
1Institutes of Medical Epidemiology, Biometrics and Informatics, Medical
Faculty of Martin Luther University Halle-Wittenberg, Halle (Saale), Deutschland
2Institute for Health and Nursing Science, Medical Faculty of Martin Luther
University Halle-Wittenberg, Halle (Saale), Deutschland
3Hautarztpraxis Prof.Dr. Khusru Asadullah, Potsdam, Deutschland
4Cardiac Surgery, University Hospital Halle (Saale), Halle (Saale), Deutschland
Purpose: Older patients with cancer dier regarding their biological
age, functionality, organ reserve and comorbidities. erefore, a compre-
hensive geriatric assessment (CGA) e.g. to assess physical and cognitive
functioning, nutritionals status, mood, self-care and social support is
recommended before planning oncological therapies1. In addition, a val-
id assessment of the biological age could add valuable information. To
investigate the possible benet of the autouorescence measurement of
advanced glycation endproducts in the skin (AGE value) in the clinical
context of geriatric oncology.
Methods: e Analysis of AGE data of a heterogeneous sample of older
cancer patients to generate hypotheses regarding the clinical relevance
of AGE. e AGE value of the skin was determined by autouorescence
measurement in n=100 cancer patients. Based on of age-specic refer-
ence values, AGE values were categorized as age-appropriate or pre-aged.
Descriptive analyses regarding sex, comorbidities, cancer diagnoses and
results of geriatric assessments were performed. To explore the predictive
properties of AGE values survival data were analyzed with simple Ka-
plan-Meier estimates and Cox regressions with log-rank tests.
Results: e analyses of the AGE values were performed on 97 patients
(47 women and 50 men) with a mean age of 75 ±5 years. Main cancer
sites comprised lung n = 27 (28%), hematological n = 16 (17%), breast
n = 14 (14%), head/neck n= 14 (14%), skin n = 12 (13%) and other =14
(14%). AGE values were Ø 3.1 Arbitrary Units (AU) ±0.8 (min. 1.7, max.
6.1). According to the age-specic reference values n =38 patients were
categorized as age-appropriate and n =59 as the pre-aged. e survival
time analyses indicated a survival advantage for tumor patients with high
AGE values (p = 0.036, KI =1.038- 2.937, n = 97).
Conclusions: Due to the exploratory design, the results are not general-
izable. To the best of our knowledge the result that high AGE value were
associated with a better survival of older cancer patients have so far not
been puplished elsewhere.
Reference:
1. Schmidt et al. 2017.
861
How to Deal with Senescent Patients in the Field of Visceral
Surgery?
Hans-Michael Tautenhahn 1, 2; Felix Dondorf 1; Philipp Felgendre 1, 2;
Astrid Bauschke 1; Uta Dahmen 1; Falk Rauchfuss 1; Utz Settmacher 1
1Clinics of General, Visceral and Vascular Surgery, University Hospital Jena,
Jena, Deutschland
2Research Programme „Else Kröner-Forschungskolleg AntiAge“, University
Hospital Jena, Jena, Deutschland
Purpose: Senescence is considered a risk factor for surgery. Due to a lack
of scientic evidence, therapeutic decisions are oen based on the clini-
cal experience of the individual surgeon. e Center of Geronto-Surgery
uringia was founded to improve the outcome aer surgery for this
growing group of patients at risk. To better characterize the age-depen-
dent risk prole, we performed a retrospective analysis of the in-hospital
results aer visceral surgery performed in the last 5 years (y).
Methods: Using the clinic patient information system data from patients
being treated in our department were extracted. Out of this cohort two
groups were formed containing either patients below the age of 35y or
older than 65y of age. Using an Access database all clinically relevant pa-
rameters (e.g. age, sex, comorbidities, duration of hospital stay, complica-
tion rate…) were assembled. Statistical analyses were performed using R.
Results: e total number of patient older than 65y as well as in relation
to the cohort of patients below 35y was rising signicantly in the study
period. Geriatric surgery patients more oen suering from postoperative
complications such as cardiovascular, pulmonary or neurological com-
plications. Even the morbidity rate was signicantly higher in the older
patient cohort, no dierence was detected in the mortality rate (30days
post-operative). e length of hospital stay was signicantly longer in the
geriatric patients.
Conclusions: Facing the problem of an ageing population yet no solu-
tions are available for this complex patient cohort especially in surgery
manners. Keeping in mind the elevated postoperative morbidity avoiding
a higher postoperative mortality is one of the challenging problems in the
eld of geriatric surgery. In our mind it is ethically not feasible to refuse
an operation in elderly patients in principle. On the other hand; these el-
derly patients are in need for an individual pre-; peri- and postoperative
course. e formation of geriatric surgery units is one promising way to
treat these patients optimized.
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2018
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2018
Gynecological Cancer
Best-of-Abstracts-Vorträge
523
Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab
(CD-Bev) vs. Carboplatin/Gemcitabine/Bevacizumab (CG-BEV)
in Patients with Recurrent Ovarian Cancer: a Prospective
Randomized Phase iii Engot/GCiG-Intergroup Study (Ago
Study Group, Ago-AUSTRiA, ANZGOG,GiNECO, SGCTG)
Lars Hanker 1; Philipp Harter 2; Jalid Sehouli 3; Jörn Rau 4; Ulrich Canzler 5;
Barbara Schmalfeldt 6; Falk Thiel 7; Ahmed El-Balat 8; Frederik Marmé 9;
Nikolaus De Gregorio 10; Klaus Baumann 11; Sven Mahner 12;
Werner Meier 13; Tjoung-Won Park-Simon 14; Eva-Maria Grischke 15;
Peter Hillemanns 14; Felix Hilpert 16; Hans-Joachim Lück 17; Rainer Kimmig 18;
Martina Gropp-Meier 19; Alexander Burges 12; Christian Jackisch 20;
Willibald Schröder 21; Jacobus Psterer 22
1Universitätsfrauenklinik Lübeck; 2Klinikum Essen Mitte
3Charite Berlin; 4KKS Marburg
5Universitätsfrauenklinik Technische Universität Dresden
6Universitätsfrauenklinik Hamburg Eppendorf
7Universitätsfrauenklinik Erlangen
8Universitätsfrauenklinik Frankfurt
9Universitätsfrauenklinik Heidelberg
10Universitätsfrauenklinik Ulm
11Klinikum der Stadt Ludwigshafen am Rhein
12Universitätsfrauenklinik München Großhadern
13Evangelisches Krankenhaus Düsseldorf
14Medizinische Hochschule Hannover
15Universitätsfrauenklinik Tübingen
16Universitätsfrauenklinik Kiel
17Gynäkologisch Onkologische Praxis Hannover
18Universitätsfrauenklinik Essen
19KH St. Elisabeth Ravensburg
20Sana Klinikum Oenbach
21Onkologikum Bremen
22Zentrum für Gynäkologische Onkologie Kiel
Purpose: In patients with recurrent ovarian cancer (ROC) suitable for
platinum based retreatment (PBT) standard therapy comprises CG-BEV
and Carboplatin(C)/pegylated liposomal-Doxorubicin (D). CG-BEV sig-
nicantly increases progression-free-survival (PFS) over CG alone whilst
CD has one of the best therapeutic indices for ROC-PBT. e aim of this
trial was to evaluate whether CD is superior to CG when given in combi-
nation with BEV with investigator-determined PFS as primary objective.
Methods: Between 2013 and 2015 682 pts. with ROC-PBT were random-
ized to CG-BEV (n=337) or CD-BEV (n=345). Secondary objectives were
overall survival (OS), biological progression-free survival (PFSBIO) by
serum CA125, quality of life (QoL) assessed by EORTC-QLQ-C30 and
QLQ-OV28, safety and tolerability.
Results: Mean age was 61.1 (SD 10.3) years, 87.4% had serous histology, 83.1%
were high grade, 41.5% were pretreated with BEV as part of rst-line treatment.
CG-BEV was associated with 359 (53.3%) serious adverse events vs. 314 (46.7%)
for CD-BEV (p=0.083). Median PFS in the standard arm CG-BEV was 11.7
months (95% CI 11.1-12.8) vs. 13.3months (95% CI 11.7-14.3) in the arm CD-
BEV (HR 0.80; 95% CI 0.68-0.96, p=0.0128). Median OS in the standard arm
CG-BEV was 27.9 months (95% CI 25.6-30.3) vs. 32.0 months (95% CI 26.6-
34.9) for CD-BEV (HR 0.810; 95% CI 0.668-0.983, p=0.0319).
In the stratum with previous anti-angiogenic treatment (n=309) median
PFS was 10.1 months (95% CI 8.5-11.2) for CG-BEV vs. 11.3 months (95%
CI 10.1-13.8) for CD-BEV (HR 0.73; 95% CI 0.57-0.94, p=0.0126).
Conclusions: CD-BEV provided a signicant PFS improvement compared
to CG-BEV in patients with ROC suitable for PBT and resulted also in supe-
rior OS compared to CG-BEV. CD-BEV was associated with fewer serious
adverse events. e global Quality of life status was not worsened by CD-
BEV. us CD-BEV is a new standard of care for patients with ROC PBT.
Disclosure Statement: ere are no disclosures.
Vorträge
265
Prevalence of BRCA1 and BRCA2 Mutations in Patients with
Primary Epithelial Ovarian Cancer Based on Family History of
Breast and Ovarian Cancers using The German Checklist – a
Single Center Experience
Beyhan Ataseven 1, 2; Denise Tripon 1; Philipp Harter 1; Stephanie
Schneider 1; Kerstin Rhiem 3; Florian Heitz 1, 4; Sonia Prader 1; Thais Baert 1, 5;
Alexander Traut 1; Nina Pauly 1; Sarah Ehmann 1; Enzo Ricciardi 1;
Helmut Plett 1; Rita Katharina Schmutzler 3; Andreas du Bois 1
1Kliniken Essen-Mitte, Department of Gynecology and Gynecologic Oncology,
Essen, Deutschland
2LMU München, Department of Obstetrics and Gynecology, University Hospital,
München, Deutschland
3Uniklinik Köln, Center for Hereditary Breast and Ovarian Cancer, Center for
Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne,
Köln, Deutschland
4Charité – Universitätsmedizin Berlin, Department of Gynecology, Campus
Virchow Clinic, Charité Medical University, Berlin, Berlin, Deutschland
5Universität Leuten, Department of Oncology, Laboratory of Tumour
Immunology and Immunotherapy, ImmunOvar Research Group, KU Leuven,
Leuven, Belgien
Purpose: BRCA1/2 are the major susceptibility genes involved in heredi-
tary epithelial ovarian cancer (EOC). Genetic testing for EOC pts in Ger-
many was recommended if validated family history (FH) based criteria
were fullled that confer a probability of a pathogenic BRCA1/2 mutation
>10%. e German checklist (CL) is a scoring tool developed and further
validated by the consortium based FH criteria including type of cancer
and ages at diagnosis of a detailed 3-generation FH. In the past, pts with
EOC lacking a FH (singular EOC) were not classied at risk according
to the checklist. Since results of the AGO TR1-study revealed mutation
prevalences of >10% also in singular EOC patients irrespective of the fa-
milial predisposition, testing is now recommended in all pts with EOC
by the German S3 guideline. Our aim was to evaluate the prevalence of
BRCA1/2-mutation(s) by CL score.
Methods: Between 01/11-05/19 1206 primary EOC pts were treated at
Kliniken Essen-Mitte. A total of 537 patients were tested for BRCA1/2
only (cohort A), in 445 cases multigene testing (TruRisk® panel) including
non-BRCA genes was performed (cohort B). For each pts, the CL score
was evaluated based on personal and familial BC/OC history.
Results: In cohort A, 23.6% (127/537) of pts had a BRCA1 (n=92) or
BRCA2 (n=35) mutation. In cohort B, 6.2% (22/356) of the patients without
BRCA1/2-mutation had other mutation (RAD51C (6), BRIP1 (4), PALB2 (3),
MSH6 (2), RAD51D (2), others (5). In 40.6% (218/537) of the pts the CL score
was 2 (singular EOC). e prevalence for BRCA1/2 mutation in cohort A was
11.0%, 17.4%, 25.5%, 35.1%, 51.4%, and 66.7% for pts with CL score 2, 3, 4, 5,
6, and ≥7, respectively. e prevalence for total mutations in the panel testing
cohort B was 15.3%, 16.7%, 28.6%, 39.1%, 44.8%, and 62.5% for pts with CL
score 2, 3, 4, 5, 6, and ≥7, respectively.
Conclusions: e BRCA1/2 mutation prevalence in EOC pts positively
correlated with increasing CL scores. However, the prevalence of muta-
tion was >10% even in singular EOC cases conrming the necessity for
oering genetic panel testing independent of FH to all pts with EOC.
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2018
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2018
Poster
211
Olaparib Routine Clinical Practice in Germany – Interim
Results of The Non-Interventional C-Patrol Study with a Focus
on Patients who Switched from The Olaparib Capsule to the
Tablet Formulation
Jacek P. Grabowski 2; Frederik Marmé 3; Felix Hilpert 4; Manfred Welslau 5;
Andreas Hartkopf 6; Ahmed El-Balat 7; Regina Glowik 8; Jalid Sehouli 9
1Universitätsmedizin Berlin Charité , Klinik für Gynäkologie, Campus Virchow
Klinikum, Berlin, Deutschland
1Universitätsmedizin Berlin Charité , Klinik für Gynäkologie, Campus Virchow
Klinikum, Berlin, Deutschland
3Universitätsklinikum Mannheim, Frauenklinik, Mannheim, Deutschland
4Onkologisches Therapiezentrum am Krankenhaus Jerusalem, Hamburg ,
Deutschland
5Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaenburg,
Aschaenburg, Deutschland
6Universitäts-Frauenklinik Tübingen, Department für Frauengesundheit,
Tübingen, Deutschland
7Universitätsklinikum Frankfurt, Klinik für Frauenheilkunde und Geburtshilfe,
Frankfurt am Main, Deutschland
8AstraZeneca GmbH, Oncology, Wedel, Deutschland
9Universitätsmedizin Berlin Charité, Klinik für Gynäkologie mit Zentrum für
onkologische Chirurgie, Berlin, Deutschland
Purpose: Olaparib (50 mg hard capsules, HC) was the 1st PARP inhibitor
approved in the EU in 12/2014 as monotherapy for maintenance treat-
ment of adult patients (pts) with platinum-sensitive relapsed BRCA-mu-
tated ovarian cancer (PSR-OC) who are in response to platinum-based
chemotherapy. In addition, lm-coated tablets (FT, 100/150 mg) were ap-
proved in the EU in 05/2018 regardless of BRCA status. Here, we report
real-world olaparib treatment data from pts who switched from olaparib
HC to FT.
Methods: e German prospective, non-interventional study C-PATROL
collects real-world clinical and patient-reported data of pts treated with
olaparib according to label. Data of 255 pts were analyzed in this interim
analysis (data cut-o: 01 April 2019) using descriptive statistics.
Results: e most commonly used olaparib HC starting dose was 800 mg
(in 85% of pts with HC (n=177), and in 77% of pts who started on HC and
switched to FT (n=47)). Most pts who started olaparib FT maintenance
therapy (n=28) received an initial daily dose of 600 mg olaparib (89%).
At the switch from the capsule to the tablet formulation, most pts started
with a FT daily dose of 600 mg olaparib (68%). In the 3 subgroups (HC,
switcher, FT), the median treatment duration was 9, 17.4 and 2.9 months,
respectively. Adverse events (AEs) ≥ grade 3 occurred in 38% (HC), 32%
(switcher) and 18% (FT) of patients; and AEs leading to discontinuation
of olaparib therapy in 11% (HC), 0% (switcher) and 7% (FT).
Conclusions: is interim analysis provides rst RWE data for the switch
from olaparib capsule to tablet formulation. e data indicate that switch-
ing was well tolerated by pts under routine conditions. e observed
toxicity prole is in line with data from clinical trials and prior interim
analyses of this study with olaparib as maintenance therapy in PSR-OC
and primary advanced OC.
Disclosure Statement: Study funded by AstraZeneca
Frederik Marmé: honoraria received for speaker, consultancy or advisory role,
travel, from AstraZeneca, Tesaro, Roche, Novartis, Pzer, PharmaMar, Genomi-
cHealth, CureVac, Amgen, Eisai, MSD,Celgene, Clovis
Felix Hilpert: Honoraria: Astra Zeneca, Clovis, Roche, Tesaro, MSD, PharmaMar,
Pzer, Novartis
Advisory Board: AstraZeneca, Roche, Tesaro, Clovis, MSD, PharmaMar
Manfred Welslau: No conict of interest
Andreas Hartkopf: Andreas Hartkopf has received honoraria (speakers bureau and
consulting fees) from AstraZeneca, Eisai, GenomicHealth, Lilly, MSD, Novartis,
Pzer, Roche, Tesaro, Teva.
Ahmed El-Balat: Ahmed El-Balat: membership on advisory councils, speaker’s
activities for AstraZeneca, Roche, PharmaMar, Olympus
Regina Glowik: Angestellte der Firma AstraZeneca
Jalid Sehouli: J. Sehouli: Advisory and expert activities for PharmaMar, Clovis,
Tesaro, Roche, Roche Diagnostics, Astra Zeneca,Merck, Bayer,Eisei, Johnson
and Johnson, MSD, Novocure, Amgen, Lilly; Receipt of professional fees from
PharmaMar, Clovis, Tesaro, Roche,Astra Zeneca, receipt of research grant support
(institution) from PharmaMar, Clovis, Tesaro, Roche, Astra Zeneca, Medimmune,
Bristol Myers, Lilly.
360
G Protein-Coupled Estrogen Receptor (GPER-1) and Agonist
G-1 Inhibit Growth of Ovarian Cancer Cells by Activation of
Anti-Tumoral Transcriptome Responses
Susanne Schüler-Toprak; Oliver Treeck; Tanja Ignatov; Atanas Ignatov;
Olaf Ortmann
Regensburg, Department of Obstetrics and Gynecology, University Medical
Center Regensburg, Regensburg, Deutschland
Purpose: Previous studies addressing the role of G-protein coupled es-
trogen receptor (GPER-1) in ovarian cancer yielded contradictory results.
On the one hand, GPER-1 was suggested to act as tumor suppressor; on
the other hand, this receptor was reported to mediate oncogenic eects on
ovarian cancer cells in vitro and to predict poor survival of ovarian cancer
patients. e present in vitro study intended to further elucidate the role
of this receptor in ovarian cancer cells comparing the eects of a GPER-1
knockdown and treatment with its agonist G-1 on cell growth, apoptosis
and the transcriptome of two ovarian cancer cell lines.
Methods: GPER-1 expression in OVCAR-3 and OAW-42 ovarian cancer
cells was knocked down by RNAi. e eects on cell growth were mea-
sured by means of the uorimetric Cell Titer Blue assay and on the tran-
scriptome by Aymetrix GeneChip analysis.
Results: Knockdown of GPER-1 and treatment with its agonist G-1 ex-
erted converse eects on growth and the transcriptome of ovarian cancer
cells. GPER-1 knockdown resulted in a signicant growth stimulation
of both cell lines, with a maximum increase by 37% (OVCAR-3) or 28%
(OAW-42), (both p<0.01). In contrast, treatment with GPER-1 agonist
G-1 decreased growth of both cell lines in a dose-dependent manner, with
a maximum inhibitory eect of 1 µM of this drug of about 80% 6 days
aer treatment. To address the question of o-target actions of this high
G-1 concentration, we found both GPER-1-dependent and -independent
eects on the transcriptome. Generally, treatment with this drug led to
a transcriptome response associated with growth inhibition. In contrast,
knockdown of GPER-1 exerted opposite eects, stimulating pathways
activating mitosis, transcription and translation, but inhibiting pathways
associated with apoptosis or interferon signaling.
Conclusions: Our data suggest that GPER-1 is able to inhibit growth of
ovarian cancer cells and support the hypothesis that this gene acts as a tu-
mor suppressor. Further studies are required to examine the signicance
of our data in the in vivo situation.
371
Revised FIGO Classication for Cervical Carcinoma
2019 - What´s New and What are the Problematis Issues?
Lars-Christian Horn 1; Christine E. Brambs 2; Anne Kathrin Höhn 1
1Institut für Pathologie, Universitätsklinikum Leipzig AöR, L
2Frauenklinik des Klinikums rechts der Isar , Technische Universität, München,
Deutschland
Purpose: Numerous therapeutic and prognostic studies of cervical carci-
noma have made a revision of the FIGO classication necessary.
Methods: Evaluation of the new FIGO classication and comparison with
previous classication dated back on 2009 und with the current TNM
classication from 2017.
Results: For microinvasive carcinomas, the horizontal dimension is no
longer considered, and diagnosis and staging will solely be made by the
depth of cervical stromal invasion. Lymphovascular invasion beyond the
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deepest point of stromal inltration by tumor cells does not alter the stage.
ere will be a new subclassication of macroinvasive carcinoma conned
to the uterine cervix which will be made by largest tumor extension as
followed: FIGO IB1/T1b1: invasive carcinoma >0.5cm depth of stromal
invasion and <2cm in largest dimension, FIGO IBII/T1b2: invasive carci-
noma >2cm and <4cm, FIGO IBII/T1b3: invasive carcinoma >4cm. Pelvic
as well as para-aortic lymph nodes will be dened as regional nodes. Pel-
vic lymph node metastases only will be categorised as FIGO IIIC1/pN1a
and para-aortic lymph node involvement with or without concomitant
pelvic involvement will be FIGO IIIC2/pN1b. Uterine corpus as well as
adnexal involvement are disregarded for staging purpose as they does not
alter itself either the prognosis or the management at time.
Conclusions: the new denition of microinvasive carcinoma may result
in stage migration which impact treatment decisions. e same issue will
occur for the denition of regional lymph nodes. An open question is still
the classication of ovarian involvement.
Disclosure Statement: ere are no disclosures.
373
Mesonephric-Like Endometrial Carcinoma May Represent an
Aggressive Tumor with Characteristic KRAS-Mutation
Lars-Christian Horn; Tina Unger; Irene Krücken; Anne Kathrin Höhn
Institut für Pathologie, Universitätsklinikum Leipzig AöR, Leipzig, Deutschland
Purpose: Very rarely mesonephric-like features are seen in ACs of the
endometrium and account for about 1% of all endometrial AC. Here we
report three cases with clinical, histopathological and molecular analyses.
Methods: Case description with immunohistochemical and molecular
analyses. Review of the literature of mesonephric-like AC of the endome-
trium for porgnosis.
Results: e mean age of the patients was 60.0 years (range range 31 to 91
years). Vaginal bleeding is the leading symptom. More than 50% showed
local advanced disease, i.e. >FIGO stage II, one third lymph node involve-
ment. About 10% of the patients died of the disease and 40.0% were alive
with evidence of the disease. Most common site of distant recurrent dis-
ease was pulmonary. Positive immunostaining of at least two of the meso-
nephric markers, like CD 10, GATA-3 and TTF with negative results for
ER and PR allows the correct diagnosis in line with mixed growth patterns
on H&E. Almost all cases represented KRAS-mutation at codon 12.
Conclusions: Uterine ML-AC are likely of Müllerian origin but represent
mesonephric features at the histopathologic, immunophenotypic and mo-
lecular level. e immunohistochemical panel of GATA-3, TTF-1, CD 10
(luminal staining), calretinin, p53 and p16 in addition to KRAS-mutation
allows the correct diagnosis of ML-AC in the majority of cases. ML-AC
may represent an aggressive subtype of endometrial cancer with pulmo-
nary involvement.
Disclosure Statement: ere are no disclosures.
417
The Use of miRNA in the Early Detection of Cervical
Intraepithelial Neoplasia
Leonore Weikert; Julia Wittenborn; Jochen Maurer; Elmar Stickeler
Uniklinik RWTH Aachen, Klinik für Gynäkologie und Geburtsmedizin, Aachen,
Deutschland
Purpose: Today, one of the biggest challenges in cancer therapy and
prevention is the latter, which includes the diculty to predict progression
of early lesions or pre-stages to invasive disease. In this context, the
characterization and categorization of pre-neoplastic lesions of squamous
cell carcinoma called cervical intraepithelial neoplasia (CIN) is an
important task.
Methods: Using small molecular markers extracted from cervical mucus
saves the patient the discomfort of a colposcopy with biopsies. We utilized
miRNAs extracted from cervical mucus samples from healthy patients
and patients with CIN 3 lesions.
Results: We can show that miRNA analysis from cervical mucus of 49 pa-
tients allowed us to distinguish between healthy patients and patients with
a CIN 3 lesion. e miRNA panel used in combination allowed for highly
signicant testing (p<0,0001) of CIN 3 status. In parallel, HPV status of
the patients, which is an important criteria for screening as well as treat-
ment strategies in the therapy of cervical cancer, signicantly correlated
with the miRNA markers hsa-miR-26b-5p, hsa-miR-191-5p and hsa-miR-
143-3p, a subpanel of the original six miRNAs.
Conclusions: We provide here the rst proof-of-concept for a cervical
mucus-based testing for pre-neoplastic stages of cervical squamous cell
carcinoma.
Disclosure Statement: no conict of interest
423
Histotype-Specic Analysis of Acid Ceramidase Expression
in Ovarian Cancer
Ahmed El-Balat; Sven Becker
Uniklinikum Frankfurt am Main, Frankfurt am Main, Deutschland
Purpose: Acid ceramidase (ASAH1) is a key player in sphingolipid me-
tabolism and signalling. It has prognostic value for several cancers, but
histotype-specic analyses of ovarian cancer are not yet available.
Methods: We used three retrospective TMA cohorts encompassing a to-
tal of 1106 ovarian cancers with follow up data for immunohistochemical
analysis of acid ceramidase (ASAH1) expression. Patients with sub-opti-
mal debulking and persistent residual tumor aer surgery introduced bias
in the prognostic analysis and were excluded from further studies.
Results: Overall, we detected an association of ASAH1 expression with
improved prognosis in ovarian cancer patients. ASAH1 expression dif-
fered between histological ovarian cancer histotypes with most frequent
expression in endometrioid and clear cell ovarian cancer, which are both
associated with good prognosis. Stratied subgroup analyses within these
histotypes did not reveal signicant survival dierences, but the power of
the analysis may be limited by smaller sample sizes. In contrast to breast
cancer, we found only a modest concordance between estrogen receptor
status and ASAH1 expression within the endometrioid ovarian cancer
histotype. In an exploratory analysis of estrogen receptor negative endo-
metrioid ovarian cancer, ASAH1 expression was associated with signi-
cantly improved overall survival (P=0.007).
Conclusions: Acid ceramidase is most frequently expressed in endome-
trioid and clear cell histo-types and could add independent prognostic
value to estrogen receptor in endometrioid ovarian cancer. Modulating
sphingolipid metabolism may lead to novel therapeutic intervention strat-
egies for this disease.
Disclosure Statement: Nothing to disclose.
425
Claudin1 Expression in Border Line Epithelial Tumors
of the Ovary
Ahmed El-Balat; Sven Becker
Uniklinikum Frankfurt am Main, Frankfurt am Main, Deutschland
Purpose: To evaluate the integral transmembrane protein Claudin 1 as
marker for borderline ovarian tumors (BOTs).
Methods: We analyzed a retrospective cohort of 114 BOTs with vali-
dated diagnosis by an independent pathologist. Immunohistochemical
detection of Claudin 1 was quantied as combined immunoreactive score
blinded to clinical patient data. Analyses were performed for Claudin 1
positive versus negative.
Results: We detected Claudin 1 positivity in 26.3% of patients. ere
was no signicant correlation between the dierent histological subtypes
and Claudin 1 expression. e expression of Claudin1 was less frequent
in patients with FIGO Stage I (p<0.045). Claudin1 expression was more
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frequent in cases with micropapillary pattern (p=0.047) and was highly
associated with the presence of implants (p=0.003).
Conclusions: Our analysis links Claudin 1 with micropapillary pattern.
Positive expression is associated with the presence of implants, which is
related to elevated risk of recurrence. Accordingly, Claudin 1 is an inter-
esting marker and worth further analyses of its prognostic value in BOTs.
Disclosure Statement: Nothing to disclose.
478
Inuence of Lymph Node Status and Treatment Strategy
on Overall Survival in Advanced Cervical Cancer
Stella Knobloch 2; Thomas Papathemelis 3; Michael Gerken 2;
Anton Scharl 3; Michael Anapolski 4; Atanas Ignatov 1; Olaf Ortmann 1;
Elisabeth C. Inwald 1; Madeleine Hetterich 1; Sophia Scharl 5;
Monika Klinkhammer-Schalke 2
1Department of Obstetrics and Gynecology, University Medical Center
Regensburg, Caritas Hospital St. Josef Regensburg, Regensburg, Deutschland
2Tumor Center, Institute for Quality Management and Health Services Research,
University of Regensburg, Regensburg, Deutschland
3Department of Obstetrics and Gynecology, Klinikum St. Marien Amberg,
Amberg, Deutschland
4Department of Obstetrics and Gynecology, University of Witten-Herdecke,
KKH Dormagen, Dormagen
5Department of Radiation Oncology and Radiotherapy in the Klinikum rechts
der Isar, Technische Universität München (TUM), München
Purpose: e lack of prognosis data hinders the implementation of an
optimal therapy for cervical cancer. Because surgery is associated with
higher morbidity, we examined the overall and relapse-free survival aer
various treatments in patients with cervical carcinoma in the FIGO stages
IIB, IIIA, IIIB and IVA with or without aected lymph nodes using data
from a clinical cancer registry in a retrospective cohort study.
Methods: Between 2002 and 2015, the Register of the Tumor Center Re-
gensburg documented 389 patients with cervical carcinoma in the FIGO
stages IIB, IIIA, IIIB and IVA. e results of the Kaplan-Meier analyzes
were given in 5-year survival and recurrence probabilities as well as the
median survival time. We estimated the hazard ratios for overall survival
aer various therapies with univariable and multivariable Cox regression
for risk adjustment.
Results: We have demonstrated the need for a thorough assessment of
lymph node status in order to obtain reliable data for the treatment strate-
gy. Our analysis showed signicant dierences in overall survival in FIGO
IIB as a function of therapy and nodal status. Overall survival was lower
with radiochemotherapy without surgery for patients with N0 compared
to a combination of surgery and chemoradiotherapy (HR = 3.012, 95%
CI 1.075 - 8.441, p = 0.036). However, in patients with aected lymph
nodes (N1), chemoradiation without surgery resulted in a comparable re-
sult (HR = 0.808, 95% CI 0.188 - 3.403, p = 0.765), while surgery alone
resulted in a poor outcome (HR = 2.889, 95% CI 1,356 - 6,156, p = 0.006).
Regardless of nodal status, advanced cervical cancer chemotherapy (FIGO
III) was superior to surgery.
Conclusions: Our study indicates that FIGO IIB patients with cervical
cancer benet from a combination of surgery and chemoradiotherapy for
long-term oncologic outcome. In the case of a lymph node involvement,
however, surgery did not result in improvement of overall survival. In pa-
tients with stage FIGO III disease chemotherapy shows the best results.
Disclosure Statement: e authors declare no conict of interest.
485
Is there an Advantage of Lymphadenectomy for Overall and
Recurrence-Free Survival in Endometrial Carcinoma Type
I FIGO IB G1-2? A Retrospective Population-Based Cohort
Analysis
Dunja Hassas 1; Thomas Papathemelis 2; Michael Gerken 1; Sophia Scharl 3;
Anton Scharl 2; Michael P. Lux 4; Mathias W. Beckmann 5; Olaf Ortmann 6;
Monika Klinkhammer-Schalke 1
1Tumor Center, Institute for Quality Management and Health Services Research,
University of Regensburg, Regensburg, Deutschland
2Department of Obstetrics and Gynecology, Klinikum St. Marien Amberg,
Amberg, Deutschland
3Department of Radiation Oncology and Radiotherapy in the Klinikum rechts
der Isar, Technische Universität München (TUM), München, Deutschland
4Frauen- und Kinderklinik St. Louise, Paderborn
5Gynecological University Cancer Center Franken, Gynecological Clinic,
University Hospital Erlangen, CCC Erlangen-EMN, Friedrich-Alexander University
Erlangen, Erlangen, Deutschland
6Department of Obstetrics and Gynecology, University Medical Center
Regensburg, Caritas Hospital St. Josef Regensburg, Regensburg, Deutschland
Purpose: e recommended therapy for patients with type I FIGO IB
endometrial carcinoma is hysterectomy and adnexectomy. However, the
therapeutic benets of additional pelvic and para-aortic lymph node dis-
section (LND) are still under discussion. In this study, we retrospectively
studied overall survival (OAS) and relapse-free survival (RFS) in patients
with endometrial carcinoma type I FIGO IB who have undergone a sys-
tematic or elective lymphadenectomy compared to patients without LND.
Methods: We included 299 patients from the registry database of the Re-
gensburg Tumor Center, who were diagnosed with endometrial adeno-
carcinoma of type I FIGO IB between 1998 and 2015. A multivariable
Cox regression was applied to the selected patient data and the hazard
ratios for OAS and RFS for the interventions performed were estimated.
Furthermore, we have made risk adjustments with respect to clinicopath-
ological parameters.
Results: We observed signicant benets of LND in univariable survival
without risk adjustment. However, we have not seen this eect conrmed
in the multivariable regression analysis aer risk adjustment. In this case,
the hazard ratio (HR) for OAS in patients without LND decreased to
1.214 (95% CI 0.771-1.911, p = 0.402) compared to patients with LND,
the HR for RFS to 1.059 (95% CI 0.689). 1.626, p = 0.795). Similarly, a
benet of systematic versus elective LND aer risk adjustment could not
be conrmed.
Conclusions: Contrary to previous observations in patients with high-
grade endometrial carcinoma, our study provides evidence that LND, and
in particular systematic lymphadenectomy, is not benecial in patients
with type I FIGO IB endometrial carcinoma in terms of overall and re-
currence-free survival.
Disclosure Statement: e authors declare no conict of interest.
491
Prognostic Factors and Outcomes of Cervical Cancer Patients
(2007-2016): a Population-Based Analysis
Miriam Rottmann; Gabriele Schubert-Fritschle; Jutta Engel
Tumorregister München (TRM), Bayerisches Krebsregister - Regionalzentrum
München (LGL), am Klinikum der Universität München, Institut für Medizinische
Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-
Maximilians-Universität (LMU) , München, Deutschland
Purpose: Cervical cancer incidence is decreasing both globally and in
Germany. e objective of this study was to analyse prognostic factors
and outcomes of invasive cervical cancer in a population-based setting.
Methods: 2,291 cervical cancer patients diagnosed between 2007 and
2016 within the catchment area of the Munich Cancer Registry (MCR)
were analysed regarding prognostic factors and outcomes. Cumulative in-
cidence was used to calculate time to locoregional recurrence and distant
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metastases. Survival was assessed using the Kaplan–Meier method, rela-
tive survival (RS) analysis, and a Cox proportional hazards model.
Results: e majority (48.7%) of the comparatively young (median age:
52 years) cervical cancer patients was diagnosed at an early tumor stage
(IA1,IA2,IB1), while 14.3% presented with metastatic disease at the time
of diagnosis. e proportion of patients with positive lymph nodes in-
creased with stage, with no lymph node involvement in stage IA1, and
up to 42.8% in stage IIB. e analysis of time to locoregional recurrence
and metastasis showed a respective 5-year cumulative incidence rate of
10.1% and 13.4%. ere was only a slight improvement in overall (5-year:
68.1%) and relative (5-year: 71.5%) survival rates over time. Stratied by
stage the 5-year overall survival ranges from 98.9% in stage IA1, to 61,6%
in IIB, and 16,6 % in patients with metastases (M1). A cox model revealed,
as expected, a statistically signicant association of age (p<0.001), stage
(p<0.001), grade (p<0.01), lymph vessel invasion (p<0.01), and histology
(p<0.01) with survival.
Conclusions: e prognosis in cervical cancer is comparatively good,
caused by the high percentage of patients diagnosed at an early stage. Un-
fortunately there is only a slight improvement in prognosis over time.
493
Trends in Prognostic Factors and Outcomes of Ovarian Cancer
Patients Over a 20-Year Period (1997-2016)
MiriamRottmann 1; Alexander Burges 2; Sven Mahner 2;
Christine E. Brambs 3; Marion Kiechle 3; Martin Pölcher 4; Dieter Grab 5;
Christoph Anthuber 6; Andreas Schnelzer 7; Franz Edler von Koch 8;
Doris Mayr 9; Wilko Weichert 10; Gabriele Schubert-Fritschle 1; Jutta Engel 1
1Tumorregister München (TRM), Bayerisches Krebsregister - Regionalzentrum
München (LGL), am Klinikum der Universität München, Institut für Medizinische
Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-
Maximilians-Universität (LMU), München, Deutschland
2Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der
Universität München, München, Deutschland
3Frauenklinik rechts der Isar, Universitätsklinikum Rechts der Isar der
Technischen Universität München (TUM), München, Deutschland
4Rotkreuzklinikum München Frauenklinik, München, Deutschland
5Klinik für Frauenheilkunde, Geburtshilfe und Chirurgie, München Klinik
Harlaching, München, Deutschland
6Klinik für Frauenheilkunde und Geburtshilfe, Klinikum Starnberg, Starnberg,
Deutschland
7Klinik für Gynäkologie und Geburtshilfe, RoMed Klinikum Rosenheim,
Rosenheim, Deutschland
8Klinik für Gynäkologie und Geburtshilfe, Klinikum Dritter Orden, München,
Deutschland
9Pathologisches Institut, Medizinische Fakultät, LMU München, München,
Deutschland
10Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische
Universität München, München, Deutschland
Purpose: Signicant eort has been made to improve the poor prognosis
of invasive ovarian cancer patients. e objective of this study was to anal-
yse prognostic factors and invasive ovarian cancer patient outcome over
time in a population-based setting.
Methods: 6,984 ovarian cancer patients diagnosed between 1997 and
2016 within the catchment area of the Munich Cancer Registry (MCR)
were analysed. Patients diagnosed 1997-2006 and 2007-2016 were com-
pared. Cumulative incidence (CI) was used to calculate time to progres-
sion. Survival was analysed using the Kaplan–Meier method (Overall sur-
vival, OS), calculation of relative survival (RS), and a Cox proportional
hazards model (OS).
Results: e incidence rate of invasive ovarian carcinoma decreased
over time from 23.8 (1997) to 16.5(2016) /100,000. e majority of the
patients continued to be diagnosed at an advanced stage of FIGO III or
IV. Furthermore, there was a slight increase (p=0.04) in the proportion
of patients diagnosed with FIGO III (45.4 vs 47.9%) and FIGO IV (23.1
vs 24.1%). While the proportion of patients that underwent surgery did
not change signicantly over time (87.0 vs 88.0%, p=0.25), an increase in
patients without residual disease was observed (50.2 vs 58.5%, p<0.001).
In patients with surgery, there was a slight improvement in time to
progression (5-year CI: 43.2 vs 41.0%, p=0.11), as well as in overall (5-
year OS: 41.2 vs 44.8%, p=0.04)) and relative (5-year RS: 44.6 vs 48.4%)
survival rates. e cox model revealed a signicant association of survival
with age (≥80 vs <50 HR 3.78, p<0.001), stage (FIGO IV vs I HR 5.54
p<0.001), residual disease (>1cm vs no residuals HR 2.09, p<0.001), and
chemotherapy (no chemo vs chemo HR 1.44, p<0.001).
Conclusions: Ovarian cancer remains a very challenging disease that
needs to be treated with highest standards. Patients undergoing successful
treatment, especially with regard to surgery, showed an improvement in
survival over time. is may primarily be due to the signicant increase
in the proportion of patients that underwent surgery without residual
disease.
497
Combined Assessment of 3Q26 Amplication and Promoter
Methylation in Patients with High Grade Cervical Lesions
Show Age Specic Dierences
Josene Beiersdorf 1; Cornelia Scheungraber 1; Kristina Wunsch 2;
Martina Schmitz 2; Alfred Hansel 2; Heike Hoyer 3; Mieczyslaw Gajda 4;
Christiane Greinke 1; Ingo B. Runnebaum 1; Claudia Backsch 1;
Matthias Dürst 1
1Klinik und Poliklinik für Frauenheilkunde und Fortpanzungsmedizin,
Universitätsklinikum Jena, Friedrich Schiller Universität, Jena, Deutschland
2oncgnostics GmbH, Jena, Deutschland
3Institut für Medizinische Statistik, Informatik und Datenwissenschaften,
Universitätsklinikum Jena, Friedrich Schiller Universität
4Institut für Rechtsmedizin, Sektion Pathologie, Universitätsklinikum Jena,
Friedrich Schiller Universität, Jena
Purpose: A considerable proportion of high grade cervical intraepitheli-
al lesions (CIN2/3) are known to resolve on their own especially among
young women. However, since reliable prognostic markers are still lack-
ing, the diagnosis “CIN3” is still an indication for surgery which may
result in overtreatment. It is conceivable that a combination of dierent,
ideally independent molecular markers may provide more reliable results.
In the present cross-sectional study two established triage markers, 3q26
amplication and a methylation signature, were evaluated in an age-de-
pendent manner.
Methods: e patient cohort comprised 60 patients with histologically
conrmed CIN2/3 in two equally sized age groups (<30 years, ≥30 years).
Cervical scrapes were analyzed by interphase uorescence in situ hybrid-
ization for 3q26 amplication and methylation specic PCR (GynTect®)
for six dierent genome regions.
Results: Both assays showed a signicantly dierent pattern of test out-
come independent of age (P=0.001). Moreover, the combination of both
assays diered signicantly for double positive and double negative cas-
es when comparing the two age groups: In patients <30 years there were
clearly less cases with positive methylation signature and amplication
of 3q26 as in women ≥30 years (23% versus 63%, Bonferroni adjusted
P=0.016). Of particular interest is the nding that double negative results
were exclusive for the young age group (0% versus 27%, Bonferroni ad-
justed P=0.020).
Conclusions: Since regression of CIN2/3 characteristically occurs among
young women it is tempting to speculate that a double negative test result
could be prognostic for regression of CIN2/3. is will have to be investi-
gated further in a prospective longitudinal intervention study.
Disclosure Statement: no conicts of interest to disclose
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2018
559
A Real-World Experience of Multiple Lines of Bevacizumab-
BASED Therapy in Patients with Pretreated Recurrent
Tuboovarian Carcinoma
Christian M. Kurbacher 1; Valérie Kallage 2; A. Tabea Kurbacher 1;
Susanne Herz 1; Alexander Schott 1; Gabriele Kolberg 1; Claudia
Schweitzer 1; Jutta Anna Kurbacher 3
1Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie I (Schwerpunkt:
Gynäkologische Onkologie), Bonn
2Frauenklinik, St. Katharinen-Hospital, Frechen
3Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie II (Allgemeine
Gynäkologie und Geburtshilfe), Bonn
Purpose: is retrospective study sought to yield more concise data on
multiple lines of Bevacizumab (Bev)-based therapy (Tx) in patients (pts)
with recurrent tuboovarian carcinoma (TOC).
Methods: 90 pts with recurrent TOC were included. 37 (41.1%) pts had
one, 20 (22.2%) had two, 13 (14.4%) had three and 20 had (22.2%) 4-9
lines of Bev. A total of 225 courses of Bev-based treatment were adminis-
tered: 58 (25.8%) as monotherapy (Bev), 63 (28.0%) in combination with
conventionally dosed Ctx (Bev+cCtx), and 104 (46.2%) in combination
with metronomic Ctx (Bev+mCtx). Time to progression (TTP) was calcu-
lated from the start of each Bev-based Tx until progression, overall surviv-
al was calculated from the start of the rst Bev-based Tx until death from
any reason or loss to follow-up. Adverse eects in regard to Bev Tx were
scored according to CTCAE vs 4.02.
Results: Bev-related G3-4 toxicities comprised hypertension in 2.2%,
bowel obstruction in 0.9%, small bowel perforation in 0.9%, nephrotic
syndrome in 0.4% and infection seen in 1.3% of treatments. Both TTP
and OS were not signicantly dierent between dierent types of Tx. TTP:
Bev, 5.4 months (ms); Bv+cCtx, 6.1 ms; Bev+mCtx, 6.3 ms. OS: Bev, 28.6
ms, Bev+cCtx, 31 ms; B+mCtx, 21.4 ms. TTP was comparable between
one and multiple lines of Bev: one line, 6.6 ms; two lines, 6.3 ms, three
lines 5.9 ms, and >4 lines 3.7 ms (p=0.130). However, OS increased sig-
nicantly with the number of Bev-based lines of Tx: one line, 8.8 ms; two
lines, 16.8 ms; three lines 25.4 ms; >4 lines, 36.6 ms (p=0.0001).
Conclusions: Retreatment with Bev is safe and eective in a real-world
population of pts with recurrent TOC. e number of Bev-based lines had
a signicant impact on overall survival.
Disclosure Statement: All authors declare no conicts of interest
637
Tissue Factor Expression of Extracellular Vesicles from
Ascites of Ovarian Cancer Patients Correlates with Venous
Thrombembolic Events (VTE)
Fanny Ender 1; Corinna Steidel 1; Nikolas von Bubno 1; Achim Rody 2;
Frank Gieseler 1
1Clinic for Hematology and Oncology, UKSH Lübeck, Lübeck, Deutschland
2Department of Gynecology, UKSH Lübeck, Lübeck, Deutschland
Purpose: As malignant eusions (e.g. ascites) contain cells, cellular com-
ponents, growth factors, and cytokines, they mirror the microenviron-
ment of tumors. Oen, patients with ovarian carcinoma suer from both
deregulated immune mechanisms and systemic hyper coagulation. As a
molecular link, tissue factor-bearing small Extracellular Vesicles (EVs)
may play a decisive role in the systemic coagulation via activation of the
extrinsic tenase as well as in tumor cell activation via the PAR2/G-pro-
tein/ERK-pathway1.
Methods: Here, we obtained ascites from ovarian carcinoma patients from
the Clinic for Gynecology of the University Medical Center Schleswig-
Holstein collected during surgery or paracentesis. EV subgroups
(exosomes, ectosomes) were isolated and separated using sequential
centrifugation as described elsewhere2. Using annexin-V coated
magnetic beads, phosphatidylserine+ EVs were specically enriched3.
EV subpopulations were then characterized using high-resolution ow
cytometry as well as electron microscopy and analyzed regarding their
procoagulant properties (PS, TF activity). Results were correlated with
clinically overt VTEs.
Results: Ascites from patients with ovarian cancer contained high
amounts of EVs that exposed varying amounts of PS and TF on their
surface. Interestingly, PS and TF were co-expressed. Isolation using an-
nexin-V coated magnetic beads resulted in a signicant enrichment of
TF+EVs. Notably, TF expression on EVs signicantly correlated with clin-
ically reported VTEs4.
Conclusions: is small study indicates the clinical value of EV diagnos-
tic in human body liquids. However, standardized methods for the isola-
tion of EV subpopulations (exosomes, ectosomes), as well as for quanti-
cation and characterization have to be used in order to get reliable and
comparable results.
References:
1. Ender et al., Anticancer Res 2019
2. Gieseler et al., Cell Biol Int 2018
3. Gieseler et al., Cell Biol Int 2014
4. Gieseler and Ender, Proceedings on Cancer-Immuno-Oncology 2018
Disclosure Statement: e Authors declare no conict of interest.
669
Analysis of Methylation Marker for Circulating Tumor DNA
of Epithelial Ovarian Cancer (EOC) – The Assurer Project
Norman Haefner; Sabrina Noack; Miriam Stein; Herbert Diebolder;
Matthias Dürst; Ingo B. Runnebaum
Universitätsklinikum Jena, Klinik für Frauenheilkunde und
Fortpanzungsmedizin, Jena, Deutschland
Purpose: e lack of early detection assays and the occurrence of un-
specic symptoms are causative for the late diagnosis of EOC. Aberrant
DNA methylation of cell-free DNA (cfDNA) may be a potential biomark-
er for EOC.
Methods: Genome wide methylation analyses of tissue-derived gDNA
and cfDNA from blood were used to identify candidate regions. Marker
validation was realized with two sample sets by methylation specic PCR
(MSP) using bisulte-treated cfDNA (set 1: benigne controls n=67 and
EOC n=68 (FIGO III/IV); set 2: EOC n=43 (FIGO I-IV) and age matched
healthy women n=14).
Results: Analyses of tissues (EOC n=33, normal ovaries n=3, white blood
cells n=4) lead to the identication of potential candidates for cfDNA
analysis. e comparison with published data resulted in the selection
of 50 candidate regions for validation. ree top candidates reached a
sensitivity and specicity of 27-57% and 91-100%, respectively. e best
two-marker combination exhibited 63.2% sensitivity and 95.5% specic-
ity. For one of these three markers a low methylation level in the tumor
tissue can explain the absence of methylation in cfDNA. Intratumoral
heterogeneity and the methylation state in early stage disease point to hy-
permethylation of one candidate as potentially late event in EOC develop-
ment. To identify additional markers the genome wide analysis of cfDNA
was established and is presently conducted.
Conclusions: e specic and sensitive detection of EOC-specic aber-
rant DNA methylation in cfDNA is possible. e direct analysis of cfD-
NA for marker identication should result in an improved diagnostic
performance to enable the early detection with DNA-methylation-based
biomarkers.
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2018
684
Safety and Eectiveness of Bevacizumab (BEV)-ContainIng
Therapy in Patients (PTS) with Primary Ovarian Cancer (OC):
Interim Analyses of The Otilia German Non-Interventional
Study
Jalid Sehouli 1; Alexander Mustea 2; Guelten Oskay-Özcelik 3; Maren Keller 4;
Rolf Richter 1; Oliver Tomé 5; Hannah Woopen 1; Ann-Kathrin Sommer 6;
Jacek Grabowski 1; Robert Armbrust 1; Pauline Wimberger 7
1Charité Campus Virchow Klinikum, Department of Gynecology with Center for
Oncological Surgery, Berlin, Deutschland
2University Hospital Bonn, Bonn, Deutschland
3Praxisklinik Krebsheilkunde für Frauen, Berlin, Deutschland
4North-Eastern-German Society of Gynaecological Oncology (NOGGO e.V.), c/o
Charité Medical University of Berlin, Berlin, Deutschland
5St. Vincentius-Kliniken, Department of Gynecology, Karlsruhe, Deutschland
6Roche Pharma AG, Grenzach-Wyhlen, Deutschland
7Carl-Gustav-Carus University Dresden, TU Dresden, Gynecology and Obstetrics,
Dresden, Deutschland
Purpose: BEV combined with carboplatin plus paclitaxel (CP) is approved
as front-line therapy for FIGO (1998) stage IIIB–IV OC. e ongoing sin-
gle-arm non-interventional OTILIA study (NCT01697488) was initiated
to assess the safety and eectiveness of front-line BEV-containing therapy
in the real-world setting in Germany. Here we present results of the 2nd
and 3rd interim analysis.
Methods: Pts with FIGO stage IIIB–IV OC received front-line BEV +
CP. Adverse events were recorded at each cycle and graded using CTCAE
v4.0. Investigators assessed response according to local practice. Patients
were followed for 12 months aer disease progression, discontinuation of
BEV or completion of 15 months of BEV therapy. Exploratory analyses
compared safety and ecacy according to age, Eastern Cooperative On-
cology Group performance status (ECOG PS), and comorbidities.
Results: 808 pts were analyzed, of whom 704 had completed documenta-
tion. Estimated median BEV treatment duration was 13.4 months (95%
CI 12.8–13.8). 433 (62%) had discontinued therapy prematurely. Median
progression-free survival (PFS) was 21.3 months (95% CI 20.3–22.5) in
the overall population. ere was no apparent dierence in PFS according
to age, ECOG PS, or between comorbidity subgroups and the overall pop-
ulation. Comorbidities were more common in pts aged ≥70 (47%) than
<70 years (53%). Tolerability was similar in subgroups aged ≥70 versus
<70 years (all grades, 74% vs. 70%; grade 3/4, 35% vs. 32%; serious AE,
31% vs. 24%).
Conclusions: e interim analyses of this large observational trial in-
dicate the favorable eectiveness and tolerability of BEV- maintenance
therapy for pts with newly diagnosed OC treated in a real-world setting.
Exploratory analyses of OTILIA showed no association of age with worse
outcome with respect to (preliminary) ecacy or tolerability. PFS results
of patients with comorbidities were in line with those of the overall pop-
ulation, despite older age and worse ECOG PS. is study underlines that
BEV is a safe and eective treatment option independently of age and co-
morbidities.
Conicts of Interest: J. Sehouli: Honoraria: AstraZeneca, Clovis Oncol, Eisai,
Johnson & Johnson, MSD Oncology, Olympus Medical Systems, Pzer, Phar-
maMar, Tesaro, Teva; Consulting or Advisory Role: AstraZeneca, Clovis Oncology,
Lilly, Merck, MSD Oncology, Pzer, PharmaMar, Tesaro; Research Funding: Astra-
Zeneca (Inst), Bayer (Inst), Clovis Oncology (Inst), Merck (Inst), MSD Oncology
(Inst), Pzer (Inst), PharmaMar (Inst), Tesaro (Inst); Travel, Accommodations,
Expenses: AstraZeneca, Clovis Oncology, MSD Oncology, PharmaMar, Roche
Pharma AG, Tesaro.
A. Mustea: Consulting or Advisory Role: AstraZeneca. Roche
G. Oskay-Özcelik: Honoraria: Roche, Novartis, AstraZeneca, AMGEN, Riemser;
MSD; Consulting or Advisory Role: Roche, Novartis, AstraZeneca, MSD
M. Keller: No Relationships to Disclose
R. Richter: No Relationships to Disclose
O. Tomé: No Relationships to Disclose
H. Woopen: Travel, Accommodations, Expenses: Medac
A.-K. Sommer: Employee of Roche
J.P. Grabowski: Honoraria: AstraZeneca, Clovis Oncology, Pzer, RIEMSER,
Roche, Tesaro. Consulting or Advisory Role: AstraZeneca, Clovis Oncology, Pzer,
RIEMSER, Roche, Tesaro; Research Funding: AstraZeneca (Inst), MSD (Inst),
RIEMSER (Inst), Tesaro (Inst); Travel, Accommodations, Expenses: Molecular
Health, Tesaro.
R. Armbrust: No Relationships to Disclose
P. Wimberger: Honoraria: Roche; AstraZeneca; Clovis Oncol; Eisai; Novartis;
Amgen; MSD; Merck; Oncology; Pzer; PharmaMar; Tesaro; Teva; Research
Funding: Amgen; Novartis; RocheConsulting or Advisory Role: Roche; MSD;
Tesaro; Novartis; Amgen; Clovis; Pzer; AstraZeneca; Eisai
691
Phase III PAOLA-1/ENGOT-OV25 Trial: Olaparib Plus
Bevacizumab (BEV) As Maintenance Therapy in Patients (PTS)
with Newly Diagnosed, Advanced Ovarian Cancer (OC) Treated
with Platinum-Based Chemotherapy (PCH) Plus Bev
Nikolaus de Gregorio 1; Philipp Harter 2; Jalid Sehouli 3; Ulrich Canzler 4;
Frederik Marme 5; Paul Buderath 6; Hans-Joachim Lück 7;
Martina Gropp-Meier 8; Ingo B. Runnebaum 9; Antje Belau 10;
Stefan Renner 11; Barbara Schmalfeldt 12; Ahmed El-Balat 13;
Alexander Burges 14; Peter Hillemanns 15; Dominik Denschlag 16;
Dirk Bauerschlag 17; Lars Hanker 18; Andreas Schnelzer 19;
Isabelle Ray-Coquard 20
1Ulm, Universitätsfrauenklinik Ulm, Ulm, Deutschland
2Klinikum Essen Mitte
3Charite Berlin
4Universitätsfrauenklinik Technische Universität Dresden, Dresden, Deutschland
5Universitätsfrauenklinik Heidelberg
6Universitätsfrauenklinik Essen
7Gynäkologisch Onkologische Praxis Hannover
8KH St. Elisabeth Ravensburg
9Universitätsfrauenklinik Jena
10Universitätsfrauenklinik Greifswald
11Universitätsfrauenklinik Erlangen
12Universitätsfrauenklinik Hamburg Eppendorf
13Universitätsfrauenklinik Frankfurt
14Universitätsfrauenklinik München Großhadern
15Medizinische Hochschule Hannover
16Hochtaunuskliniken Bad Homburg
17Universitätsfrauenklinik Kiel
18Universitätsfrauenklinik Lübeck
19Universitätsfrauenklinik rechts der Isar TU München
20Centre Léon BERARD, Lyon, Lyon, Frankreich
PAOLA-1 Study
Purpose: PAOLA-1/ENGOT-ov25 (NCT02477644) is the rst Phase
III trial to evaluate the ecacy and safety of a PARP inhibitor with bev
as rst-line (1L) maintenance therapy for advanced OC, regardless of
BRCA1/2 mutation (BRCAm) status. Please copy and paste the
Methods: PAOLA-1 is a randomized, double-blind, international Phase
III trial. Eligible pts had newly diagnosed, FIGO stage III–IV, high-grade
serous or endometrioid OC, fallopian tube or primary peritoneal cancer.
Pts had received standard PCh plus bev and were in clinical complete or
partial response. Pts were randomized (2:1) to Olaparib tablets (300 mg
bid for up to 24 months [m]) plus bev (15 mg/kg, d1, q3w, for 15 m in-
cluding when combined with PCh) or placebo (pbo) plus bev, stratied by
1L treatment outcome and tumour BRCAm status. e primary endpoint
was investigator-assessed progression-free survival in the intent-to-treat
population (PFS; modied RECIST v1.1).
Results: e primary endpoint in the intent-to-treat population showed a
statistically signicant and clinically meaningful improvement in progres-
sion-free survival (PFS). e safety and tolerability proles observed in
PAOLA-1 were generally consistent with those known for each medicine.
Conclusions: In patients with advanced primary ovarian cancer, main-
tenance Olaparib resulted in a statistically signicant PFS improvement.
is is the rst time this was demonstrated regardless of BRCA mutation
status.
Literature: not applicable
Disclosures: will be shown in the nal presentation with updated information on
disclosures of all 20 authors
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts94
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778
Laparoscopic Radical Hysterectomy in Cervical Cancer:
Is Peritoneal Contamination with Tumor Cells an
Underestimated Event?
Rüdiger Klapdor; Hermann Hertel; Peter Hillemanns;
Matthias Jentschke
Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule
Hannover, Hannover, Deutschland
Purpose: Peritoneal dissemination of cervical cancer cells during intra-
corporal colpotomy might be responsible for reduced disease free surviv-
al aer laparoscopic radical hysterectomy as shown in the LACC study.
However, data on the frequency or mechanisms of peritoneal contamina-
tion are missing. erefore, we aimed to analyze peritoneal contamination
of cervical secretion during intracorporal colpotomy with a novel indocy-
aningreen (ICG) -based technique.
Methods: In this prospective study, we evaluated patients undergoing
routine laparoscopic or robot-assisted hysterectomy for benign indica-
tions. Routine surgery was performed aer application of ICG specically
to the cervical surface. During and aer colpotomy pictures under white
and uorescence light were taken in order to evaluate frequency and ex-
tent of peritoneal contamination.
Results: Peritoneal contamination during intracorporal colpotomy oc-
curred in 9/12 (75%) patients undergoing routine laparoscopic hysterec-
tomy. Laparoscopic instruments were contaminated in 60% of all cases.
Extent of contamination varied between individual patients with a medi-
an grade of 2.75 (range 1-4.5; 1 no contamination - 5 strong contamina-
tion) at posterior colpotomy. ere were no adverse eects during surgery.
Conclusions: Peritoneal contamination with cervical secretion is a fre-
quent event during intracorporal colpotomy. We describe a promising
tool for feasible and direct visualization of peritoneal contamination
during laparoscopic colpotomy. is may be easily implemented in fur-
ther studies on laparoscopic radical hysterectomy and serve as a quality
assessment tool for surgeons and surgical techniques.
Disclosure Statement: All authors declare no conict of interest.
815
Sentinel Lymph Node Dissection in Vulvar Cancer. A Survey
About Knowledge, Status and Counseling in Outpatient
Sector
Marlene Röttger; Hermann Hertel; Peter Hillemanns; Rüdiger Klapdor
Frauenklinik, Medizinische Hochschule Hannover, Hannover, Deutschland
Purpose: Sentinel lymph node dissection is an alternative to radical
lymph node dissection (LND) for early vulvar cancer. Patient selection
and counseling is key for a safe use of SLND (1). Our aim was to evaluate
how gynecologists in an outpatient setting think about SLND, counsel pa-
tients and select hospitals for further treatment.
Methods: A questionnaire containing 29 questions about SLND in vulvar
cancer was sent to gynecologists in Lower Saxony via mail and letter. e
questionnaire contained multiple choice questions and open questions.
e study was approved by the local ethics committee.
Results: e median age of the 80 respondents was 54.5 (26-66) years.
Most (86%) participants reported to only treat one to ve patients with
vulvar cancer per year. Interestingly, 70% and 64% of the gynecologists
send their patients to university hospitals or hospitals oering maximum
care, respectively. Of all, 33% replied that SLND was performed rarely or
never in their patients. e gynecologists answered that only 40% of the
patients are well informed about advantages and possible disadvantages
of SLND. Most (95%) felt responsible to counsel patients on treatment
decisions independently from or additionally to the hospital. Of all, 78%
replied that they are not completely sure about the exact recurrence rates
aer SLND. Of notice, 68% believe that SLND for vulvar cancer is safe if
applied in specialized centers and 92% stated that focusing patients on
specialized centers is required for best results.
Conclusions: Gynecologists in the outpatient setting play a crucial role
for counseling and admission of patients to the hospitals. A close com-
munication between hospital and outpatient gynecologists appears to be
essential to select optimal treatment strategies for individual patients.
Reference:
1. Diagnosis, erapy, and Follow-Up Care of Vulvar Cancer and its Precursors.
National Guideline of the German Society of Gynecology and Obstetrics
(S2k-Level, AWMF Registry No. 015/059, August 2015).
Disclosure Statement: All authors have no conicts of interest.
837
Characterization of Tribbles 1 in Epithelial Ovarian Cancer
Leonard Bauerschmitz; Vanessa Raddatz; Matthias Dürst;
Ingo B. Runnebaum; Norman Haefner
Universitätsklinikum Jena, Klinik für Frauenheilkunde und
Fortpanzungsmedizin, Jena, Deutschland
Purpose: We have identied TRIB2 a member of the Tribbles protein
family as mediator of cisplatin sensitivity in epithelial ovarian cancer
(EOC; Ref.1). e aim of the presented project is the characterization of
Tribbles 1 (TRIB1).
Methods: Gene expression analyses of clinical samples (EOC type II,
FIGO III/IV, n=38) and cell lines were done by qRT-PCR. In-vitro analy-
ses were conducted aer stable overexpression of TRIB1 using retroviral
transduction of A2780 (parental and resistant cultures) and OVCAR3
cells. Functional readouts consist of IC50 determination against cisplatin,
proliferation and colony formation assays.
Results: TRIB1 RNA expression was signicantly higher in parental cell
lines or platin sensitive EOC patients compared to resistant sub-cultures
and patients, respectively. Moreover, parental sensitive cell lines revealed a
time and concentration dependent upregulation of TRIB1 under cisplatin
treatment, whereas resistant cells exhibited a more stable TRIB1 expres-
sion. EOC patients stratied by the median TRIB1 expression resulted
in groups with signicantly dierent PFS and OS. Patients with TRIB1-
high tumors had a longer survival than patients with TRIB1-low tumors
(p<0.05, LogRank test). e successful overexpression of TRIB1 in paren-
tal and resistant A2780 cells (>10-fold increase of transcript level) did not
result in changed IC50 values for cisplatin.
Conclusions: Although TRIB1 gene expression is potentially prognos-
tic for EOC and is aected by cisplatin exposure similarly to the TRIB2
expression, its overexpression cannot reverse the resistant phenotype
in A2780. Presently, both the validation in other EOC cell lines and the
exploration of the molecular dierences between TRIB1 and TRIB2 are
conducted.
Reference:
1. Kritsch et al. Tribbles 2 mediates cisplatin sensitivity and DNA damage respon-
se in epithelial ovarian cancer. Int J Cancer. 2017 Oct 15;141(8):1600-1614
843
Adapted Adjuvant TC Chemotherapy in Primary Tubal Cancer
After Renal Transplantation and Chronic Hepatitis
C Infection - A Case Report
Peter Ugocsai; Madeleine Hetterich; Paolo Gennari; Attila Teoman;
Atanas Ignatov; Olaf Ortmann; Stephan Seitz
Department of Gynecology and Obstetrics, University Medical Center
Regensburg, Regensburg, Deutschland
Purpose: Application of a platinum-based chemotherapy in patients with
impaired renal function or taxanes in case of liver disorders is challeng-
ing. Strategies suggested applying platinum at a GFR <15ml/min include a
dose reduction with subsequent dialysis (DIA). Considering taxanes, due
to a possible hepatitis C reactivation a close monitoring with temporary
discontinuation and subsequent dose reduction is suggested.
Methods: Presentation 74-year old patient with renal impairment follow-
ing a renal transplantation and a chronic hepatitis C infection with the
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2018
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2018
clinical picture of an ovarian cancer. Following an exploratory laparot-
omy, a primary high-grade serous fallopian tube cancer was conrmed,
FIGOIIIb, with the operative achievement of a macroscopic disease-free
status (R0). e adjuvant chemotherapy with paclitaxel (TAX) and car-
boplatin (CAR) was adapted to the impaired renal function and hepatic
status: TAX 140mg/m2, followed aer 48 hours by CAR 125mg/m2 with
a subsequent DIA aer 20 hours (AUC 3-5 mg·min/ml) (d1[TAX], d3[-
CAR], d4[DIA] / q3w).
Results: Hematotoxicity with anemia and thrombocytopenia, without
signs of leukopenia appeared aer 3 cycles resulting in a further dose
reduction of TAX. Anemia was treated with regular blood transfusions
during DIA. e treatment was discontinued aer 5 cycles due to a se-
vere thrombocytopenia. Relapse occurred aer 10 months. 2nd line treat-
ment was initiated with liposomal doxorubicin in monotherapy (d1/q4w),
which was discontinued aer 3 cycles due to a severe thrombocytopenia
and disease progression, followed by best supportive care.
Conclusions: : In case of a combined renal and hepatic impairment we
suggest during a combined TC treatment TAX in reduced dose and the
time-delayed application of CAR along with a hemato-nephroprotec-
tive dialysis within 24 hours. According to the observed hematological
toxicity of TC, apart from transfusion of red blood cells, the continuous
application of thrombopoietin during the cytotoxic treatment should be
considered.
Disclosure Statement: no conict of interest
Head and Neck Cancer
Poster
194
Nivolumab Adjuvant in Combination with Postoperative
Radiotherapy and as Maintenance in Patients with
Intermediate Risk Locally Advanced Head and Neck
Cancer – The NadiHN Trial
Franz-Georg Bauernfeind 1; Henning Schäfer 2; Matthias Hautmann 3;
Thomas Gauler 4; Rolf Mahlberg 5; Wilfried Budach 6; Balint Tamaskovics 6;
Rene Baumann 7; Michael Eble 8; Justin Hasenkamp 9; Adriane Koppelle 10;
Anke Reinacher-Schick 10; Ste Pigorsch 11; Anne Lammert 12; Lisa Meert 1;
Anca-Ligia Grosu 2; Dariusch Hadizadeh 13; Glen Kristiansen 14;
Martina Heimann 15; Andreas Dietz 16; Peter Brossart 1
1Medizinische Klinik III, Universitätsklinikum Bonn, Bonn, Deutschland
2Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg,
Deutschland
3Klinik für Strahlentherapie, Universitätsklinikum Regensburg, Regensburg,
Deutschland
4Klinik für Strahlentherapie, Universitätsklinikum Essen, Essen, Deutschland
5Medizinische Klinik I, Mutterhaus Trier, Trier
6Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum
Düsseldorf, Düsseldorf
7Klinik für Radio-Onkologie, Marien-Krankenhaus Siegen, Siegen
8Klinik für Strahlentherapie, Universitätsklinikum Aachen, Aachen
9Abteilung für Hämatologie und Onkologie, Universitätsmedizin Göttingen,
Göttingen
10Abteilung für Onkologie, Universitätsklinikum Bochum, Bochum
11Klinik für Radioonkologie und Strahlentherapie, Technische Universität
München, München
12HNO-Klinik, Universitätsmedizin Mannheim, Mannheim
13Abteilung für Radiologie, Universitätsklinikum Bonn, Bonn
14Institut für Pathologie, Universitätsklinikum Bonn, Bonn
15Abteilung für Strahlentherapie, Universitätsklinikum Bonn, Bonn
16HNO-Klinik, Universitätsklinikum Leipzig, Leipzig
Purpose: Adjuvant radiotherapy is the standard of care in postoperative
patients with locally advanced head and neck squamous cell carcinoma
(HNSCC) and adequate R0 resection in the absence of extracapsular
lymph node extension (ece). Immunotherapy with the check point in-
hibitor Nivolumab has signicantly improved the outcome of relapsed/
refractory HNSCC patients. Preclinical data suggest that the combination
of photon radiation with PD-1 targeting immunotherapies may strength-
en immune responses. is two-armed, randomized, open-label phase
II trial evaluates the ecacy of combined adjuvant immunotherapy and
radiation therapy.
Methods: 176 patients with locally advanced stage HNSCC (R0, ece-) will
be included. 88 patients will be randomized to receive standard of care
adjuvant 60 Gy IMRT (standard arm). 88 patients will additionally receive
Nivolumab (experimental arm). Nivolumab will be given once prior to
radiotherapy (RT), concurrently to RT and over 3 months every 2 weeks
aer RT. en, Nivolumab will be additionally applied as maintenance
therapy over the course of additional 9 months every 4 weeks. erapy
will be stopped in case of progression or unacceptable toxicity.
Results: e primary endpoint will be disease free survival. Secondary
endpoints will be overall survival, safety and quality of life. An extensive
exploratory translational research program attached to this trial will focus
on mechanisms of the immune-stimulating eect of radiotherapy and the
identication of potential biomarkers predicting response to Nivolumab.
40 patients have been recruited by July 2019. e detailed treatment pro-
tocol and accrual data will be presented.
Conclusions: e NadiHN trial will contribute prospective data to the
level of ecacy of adjuvant immunotherapy with Nivolumab and safety
data on the combination of photon radiation and immunotherapy with
Nivolumab in the postoperative setting where single adjuvant radiation
therapy would be the standard of care.
Disclosure Statement: EudraCT 2016-004787-20; Funding: Bristol-Myers Squibb
GmbH & Co. KGaA.
200
Oncogenic BTK Promotes Growth and Vascularization
of Head and Neck Squamous Cell Carcinoma (HNSCC) in Vitro
and in Vivo
Anna-Rebekka Staufenberg 1; Hannah Strobel 1; Kristina Lesakova 1;
Ninel Azoitei 2; Johanna Sporleder 1; Jasmin Ezić 1; Julia Kolarova 3;
Robert Drees 1; Stephanie E. Weissinger 4; Alexey Ushmorov 5;
Johannes Döscher 1; Marie-Nicole Theodoraki 1; Patrick Schuler 1;
Simon Laban 1; Ole Ammerpohl 3; Thomas K. Homann 1;
Emanuela Grassili 6; Cornelia Brunner 1
1Ulm University Medical Center, Department of Oto-Rhino-Laryngology, Ulm,
Deutschland
2Ulm University Medical Center, Department of Internal Medicine I, Ulm,
Deutschland
3Ulm University Medical Center, Institute of Human Genetics, Ulm, Deutschland
4Ulm University Medical Center, Institute of Pathology, Ulm, Deutschland
5Ulm University, Department of Physiological Chemistry, Ulm, Deutschland
6University of Milano-Bicocca, School of Medicine and Surgery, Monza, Italien
Purpose: Recently, two novel BTK (Brutons Tyrosine Kinase) isoforms
of 80 and 65 kDa have been described to be expressed in solid carcino-
ma entities and therein BTK expression seemed to be linked with tumor
growth and protection from apoptosis resulting in a poor prognosis of
these cancer patients. Until these observations, no BTK expression out-
side the hematopoietic system has been reported. erefore, we aimed to
investigate whether BTK isoforms are also expressed in HNSCC and to
further elucidate the molecular and cellular consequences of BTK expres-
sion for HNSCC tumorigenesis.
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Methods: HNSCC-derived cell lines as well as tumor samples were ana-
lyzed for BTK-p65 and –p80 expression. e consequences of pharmaco-
logical and genetic inhibition of BTK activity for proliferation, cell cycle
progression, transmigration, apoptosis and vascularization were analyzed
in vitro and in vivo. BTK-promoter methylation studies were performed.
Results: BTK-p65 and -p80 isoforms are expressed in HNSCC cell lines as
well as in primary HNSCC samples. Pharmacological or genetic targeting
of BTK activity leads to inhibition of cell proliferation, transmigration as
well as VEGF secretion in vitro. ese eects were associated with cell
cycle arrest and induction of apoptosis. Moreover, in in vivo xenogra ex-
periments, chemically abrogation of BTK activity impaired tumor growth
and was associated with decreased tumor vascularization. BTK-promoter
methylation studies revealed a regulation of oncogenic Btk expression by
epigenetic alterations.
Conclusions: Together, our data characterize BTK-p65 as well as BTK-p80
as novel HNSCC-associated oncogenes representing crucial players in the
maintenance of HNSCC. us, targeting BTK-activity appears to be a
promising therapeutic option for patients suering from BTK-expressing
HNSCC.
Disclosure Statement: Nothing to disclose
259
Hanna - Real-World Data from a Non-Interventional Study
Assessing Routine Use of Nivolumab in Patients with
Recurrent or Metastatic Cancer of the Head and Neck
(R/M SCCHN) in Germany
Manfred Welslau 1; Eyck von der Heyde 2; Thomas Gauler 3; Dennis Hahn 4;
Ulrike Bockmühl 5; Claus Wittekindt 6; Harald Müller-Huesmann 7;
Chia-Jung Busch 8; Paul-Stefan Mauz 9; Daniela Waldenberger 10;
Andreas Dietz 11
1Klinikum Aschaenburg, Hämato-Onkologische Schwerpunktpraxis,
Aschaenburg, Deutschland
2Onkologische Praxis am Raschplatz, Hannover, Deutschland
3Universitätsklinikum Essen, Klinik für Strahlentherapie, Essen, Deutschland
4Klinikum der Landeshauptstadt Stuttgart, , Stuttgart, Deutschland
5Klinikum Kassel, Kassel, Deutschland
6Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
7Brüderkrankenhaus St. Josef Paderborn, Paderborn, Deutschland
8Universitäts-Klinikum Hamburg-Eppendorf, Klinik und Poliklinik für Hals-,
Nasen- und Ohrenheilkunde, Hamburg, Deutschland
9Universitätsklinikum Tübingen, Klinik für Hals-, Nasen- und Ohrenheilkunde,
Tübingen, Deutschland
10Bristol-Myers-Squibb GmbH & Co. KGaA, München, Deutschland
11Universitätsklinikum Leipzig, Klinik und Poliklinik für Hals-, Nasen-,
Ohrenheilkunde, Leipzig, Leipzig, Deutschland
Purpose: Nivolumab (a fully human IgG4 monoclonal antibody target-
ing the PD-1 receptor on activated T-cells), is indicated in the EU for
the treatment of patients with R/M SCCHN progressing on or aer plat-
inum-based therapy. Results from CheckMate 141 (NCT02105636), the
pivotal trial evaluating nivolumab versus investigator’s choice (metho-
trexate, docetaxel, or cetuximab), demonstrated that patients treated with
nivolumab had signicantly improved overall survival (OS), higher re-
sponse rates, reduced adverse events, and maintained quality of life (QoL)
measures. e objective of this study is to assess real-world nivolumab
utilization, safety and outcomes in patients with R/M SCCHN.
Methods: HANNA is collecting real-world data on the routine treatment
of 385 patients with R/M SCCHN in 56 clinics and practices in Germa-
ny. Patients will be followed for 5 years from treatment initiation with
Nivolumab until death, withdrawal of consent, loss of follow-up/record
or to end of study. Primary objective is OS. Secondary objectives include
progression free survival, response rates, baseline characteristics, safety
proles and QoL.
Results: In this interim analysis, data of 300 patients with R/M SCCHN
regarding baseline-characteristics, eectiveness of the Nivolumab
treatment as well as safety and QoL under treatment will be presented.
e data provides information on disease and treatment characteristics,
prior treatment and ECOG performance status in an unselected patient
population.
Conclusions: Real-World data from HANNA reect use of Nivolumab in
routine clinical practice including patients with higher age and ECOG >2.
Recent results1 have shown that patients have a similar improvement in
outcomes, the treatment with Nivolumab was well tolerated and the QoL
stabilized under therapy.
Reference:
1. Dietz et al. DGHNO 2019, Oral presentation #101
Disclosure Statement: Amgen, Astellas, AstraZeneca, Bms, Celgene, Gilead,
Hexal, Janssen, Lilly, Medac, Novartis, Roche, Sano
287
Adenosine Receptor 2B Activity Promotes Autonomous
Growth, Migration As Well As Vascularization of Head
and Neck Squamous Cell Carcinoma Cells
Max Wilkat 1; Hanna Bast 1; Robert Drees 1; Johannes Dünser 1;
Magnus Brhel 1; Ninel Azoitei 2; Ralf Marienfeld 3; Felicia Frank 1;
Alexey Ushmorov 4; Jens Greve 1; Eva Goldberg-Bockhorn 1;
Marie-Nicole Theodoraki 1; Johannes Doescher 1; Simon Laban 1;
Patrick J. Schuler 1; Thomas K. Homann 1; Cornelia Brunner 1
1Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie ,
Universitätsklinik Ulm, Ulm , Deutschland
2Department of Internal Medicine I, Ulm University Medical Center
3Institute of Pathology, University of Ulm
4Department of Physiological Chemistry, University of Ulm
Purpose: Adenosine is a signaling molecule that exerts dual eects on
tumor growth: while it inhibits immune cell function, thereby prevent-
ing surveillance by the immune system, it also inuences tumorigenesis
directly via activation of adenosine receptors on tumors. However, the
mechanisms aecting oncogenic processes particularly in head and neck
squamous cell carcinomas (HNSCC) are not fully understood. e aim
was to identify the eects of ADORA2B (adenosine receptor A2B) on
HNSCC-derived cell lines.
Methods: First, the expression prole was analyzed by RT-PCR and West-
ern-Blot. Second, the eects of ADORA modulation by receptor ligands
on proliferation, migration, invasion and angiogenesis were investigated.
Also, the activity of ADORA2B was analyzed. In vitro experiments in-
volved MTT assays, scratch assays, transwell migration assays, VEGF-ELI-
SA and cAMP-Assays; in vivo experiments involved tumor xenogra on
chicken chorionallantoic membranes (CAM-Assay).
Results: Targeting ADORA2B with the inverse agonist/antagonist PSB-
603 leads to inhibition of proliferation, transmigration and VEGFA secre-
tion in vitro. At the molecular level, cell cycle arrest as well as the induc-
tion of the apoptotic pathway were found. In addition, shRNA-mediated
down-modulation of ADORA2B expression caused decreased prolifera-
tion. Moreover, in in vivo xenogra experiments, chemical and genetic
abrogation of ADORA2B activity impaired tumor growth associated with
decreased tumor vascularization.
Conclusions: We found that ADORA2B is upregulated and constitutively
active in HNSCC-derived cell lines. e receptor promotes cell growth,
migration and angiogenesis in vitro and in vivo. Our data suggest ADOR-
A2B being an important biomarker as well as an interesting therapeutic
target for treatment of HNSCC.
Reference:
1. Mello P de A, Coutinho-Silva R, Savio LEB. Multifaceted eects of extracellu-
lar adenosine triphosphate and adenosine in the tumor-host interaction and
therapeutic perspectives. Front Immunol 2017;8:1–17.
Disclosure Statement: Nothing to disclose.
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2018
Index
2018
329
Eects of Exosomes on B Cell Populations in Head and Neck
Squamous Cell Carcinoma (HNSCC)
Jan Christian Schröder; Sandra S. Jeske; Thomas K. Homann;
Cornelia Bruner; Marie-Nicole Theodoraki; Patrick J. Schuler
Department of Otorhinolaryngology, Head and Neck Surgery, University of
Ulm, Ulm, Deutschland
Purpose: e tumor microenvironment (TME) of HNSCCs is highly im-
munosuppressive. Tumor derived exosomes are key mediators of many
pro-tumorigenic eects and exhibit strong immunosuppressive proper-
ties. So far, this has been established for T cells and other leukocyte pop-
ulations, but the eects of exosomes on B cells remain to be elucidated.
Here we show that exosomes puried from the plasma of HNSCC patients
modify the phenotype of B cells.
Methods: : Exosomes were isolated from plasma of HNSCC patients by
mini size exclusion chromatography. B cells were puried from peripheral
blood of healthy donors by LeukoSep and CD19-negative selection and
co-cultured with HNSCC exosomes. Using ow cytometry, the expres-
sion of checkpoint receptors was determined. Adenosine production was
assessed by luciferase assay. e activity of the B cell receptor (BCR) path-
way was inferred by measuring the expression of phosphorylated Brutons
tyrosine kinase (p-BTK).
Results: Co-cultivation with HNSCC exosomes inhibited cluster for-
mation of stimulated B cells. is was accompanied by a decrease in the
expression of the co-stimulatory checkpoint receptor GITR and CD39,
an ATP-hydrolyzing ectoenzyme. In line with this, ATP hydrolysis and
adenosine production by exosome-treated B cells were decreased. Fur-
thermore, the expression of p-BTK was reduced.
Conclusions: ese results demonstrate that exosomes derived from HN-
SCC patients have direct eects on B cells in vitro. We suspect a global
inhibitory eect; since exosomes inhibited cluster formation; reduced the
expression of a co-stimulatory receptor and decreased the activity of the
BCR pathway.
387
Feasibility and Results of a Denitive Radiotherapy (RT) or
Chemoradiation (RCT) for Elderly Patients with Squamous Cell
Carcinoma of The Head and Neck (SCCHN) – a Retrospective
Monoinstitutional Survey
Matthias Hautmann 1; Anna Ratzisberger 2; Matthias Hipp 3; Felix Steger 1;
Tobias Ettl 4; Katja Evert 5; Oliver Kölbl 1; Christoph Süß 1
1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,
Regensburg, Deutschland
2Klinik für Psychiatrie, Bezirkskrankenhaus Passau, Passau
3Klinik für Strahlentherapie, Klinikum St. Marien, Amberg
4Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie,
Universitätsklinikum Regensburg, Regensburg
5Institut für Pathologie, Universitätsklinikum Regensburg, Regensburg
Purpose: SCCHN belong to the frequent malignancies worldwide. In an
aging society, also the incidence of SCCHN in elderly patients is rising.
Worldwide denitive RT or RCT is widely used as rst line therapy.
Nevertheless, elderly patients are underrepresented in clinical trials. e
aim of this survey was to evaluate the feasibility of a denitive RT/RCT
and the treatment results in a collective of elderly patients with SCCHN.
Methods: All patients older than 70 years, which received a denitive RT
or RCT at the University Hospital Regensburg from 2004 to 2018 were
included.
110 patients could be identied with a median age of 75 years. Most pa-
tients suered from a SCCHN UICC stadium IVa. 46 patients received a
concomitant chemoradiation, 64 patients were just irradiated. e median
pretreatment Karnofsky Performance Status was 70 %.
e median follow up was 16 months (IQR 7 to 30 months).
Results: e feasibility of radiotherapy was good. Only for 18 patients
radiotherapy had to be interrupted for more than one day. 46 % of the
patients could receive at least 75 % of the planned dose of the chemotherapy.
66 % of the patients suered from any acute toxicity of CTC grade III
or IV.
e overall survival was 59 % aer 12, 33 % aer 24 and 15 % aer 60
months. e local control was 85 % aer 12 months, 63 % aer 24 and 50
% aer 60 months.
Conclusions: We could nd a good feasibility of a denitive radiotherapy
and a reasonable feasibility of concomitant chemotherapy for elderly pa-
tients with SCCHN. Also in comparison with collectives of younger pa-
tients the overall survival is reasonable, particularly regarding the reduced
pretreatment general condition of the patients. Because of our results
concerning feasibility, a de-intensication of radiotherapy just due to age
seems not to be justied.
Disclosure Statement: On behalf of all authors, the corresponding author declares
that there are no conicts of interest.
397
The Role of Tertiary Lymphoid Structures in Adenoid Cystic
Carcinoma
Johannes Döscher 1; Simon Laban 1; Patrick J. Schuler 1;
Thomas K. Homann 1; Stephanie E. Weissinger 2
1Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie,
Universitätsklinikum Ulm, Ulm, Deutschland
2Institut für Pathologie, Universitätsklinikum Ulm, Ulm, Deutschland
Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy of sali-
vary glands in the head and neck. e prognosis remains poor and late re-
currences oen occur aer 5 years and later.1 To date, there are no reliable
prognostic markers for ACC. In several solid tumors, tertiary lymphoid
structures (TLS) are associated with improved survival. is study aims to
investigate the role of distribution patterns of tumor inltrating immune
cells (TIL) in ACC.
Methods: Our screening cohort consisted of 10 ACC patients where for-
malin-xed paran embedded (FFPE) tissue of the primary tumor were
available. e validation cohort comprised further 25 patients. All patients
were treated at the Ulm University head and neck cancer center. Sections
were stained for CD3, CD4, CD8 and CD20 and evaluated with regard to
their distribution of TIL. Patterns were determined as inltrated-exclud-
ed, inltrated-inamed and presence of tertiary lymphoid structures as
published before.2
Results: In the screening cohort 8 of 10 tumors presented with an inl-
trated-excluded TIL pattern by inltrating ≤ 5% of the tumor. Two cases
showed an inltrated-inamed phenotype with more CD3+ cells (80%
and 60%) than CD20+ (20% and 40%) and additionally formed TLS.
ese two cases had no relapse, whereas 50% of the inltrated-excluded
tumors relapsed. Due to the limited case number in the screening cohort,
these results were not statistically signicant and are currently being veri-
ed in the validation cohort.
Conclusions: TIL patterns in ACC represent a promising prognostic tool
and could identify patients at risk of relapse. ese patients should be
monitored more closely and possibly treated more aggressively.
References:
1. Lloyd S et al. (2011) Determinants and patterns of survival in adenoid cystic
carcinoma of the head and neck, including an analysis of adjuvant radiation
therapy. Am J Clin Oncol Cancer Clin Trials 34:76–81.
2. Wagner D.-C. et al. (2018). [Prognostic signicance of immune cell inltrates
in tumor pathology]. Der Pathologe, 39(6), 532–538.
Disclosure Statement: Nothing to declare.
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2018
Index
2018
410
Feasibility and Results of a Postoperative Radiotherapy (RT) or
Chemoradiation (RCT) for Elderly Patients with Squamous Cell
Carcinoma of the Head and Neck (SCCHN) – a Retrospective
Monoinstitutional Survey
Christoph Süß 1; Anna Ratzisberger 1; Matthias Hipp 2; Felix Steger 1;
Tobias Ettl 3; Katja Evert 4; Oliver Kölbl 1; Matthias Günther Hautmann 1
1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,
Regensburg, Deutschland
2Klinik für Strahlentherapie, Gesundheitszentrum und Klinikum St. Marien
Amberg, Amberg, Deutschland
3Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie,
Universitätsklinikum Regensburg, Regensburg, Deutschland
4Institut für Pathologie, Universitätsklinikum Regensburg, Regensburg,
Deutschland
Purpose: SCCHN belong to the frequent malignancies worldwide. In an
aging society, also the incidence of SCCHN in elderly patients is rising.
Nevertheless, elderly patients are underrepresented in clinical trials. e
aim of this survey was to evaluate the feasibility of a postoperative RT/RCT
and the treatment results in a collective of elderly patients with SCCHN.
Methods: All patients older than 70 years, which received a denitive RT
or RCT at the University Hospital Regensburg from 2004 to 2018 were
included.
71 patients could be identied with a median age of 75 years. Most pa-
tients suered from a SCCHN UICC stadium IVa. 9 patients received a
concomitant chemoradiation, 62 patients were only irradiated.
e median follow up was 27 months (IQR 18 to 62 months).
Results: e feasibility of radiotherapy was good. Radiotherapy had to
be interrupted for more than one day for 18 patients. 6/9 patients could
receive at least 75 % of the planned dose of the chemotherapy.
52 % of the patients suered from any acute toxicity of CTC grade III
or IV.
e overall survival was 87 % aer 12, 67 % aer 24 and 41 % aer 60
months. We could only identify the pretreatment general condition as
predictive factor for overall survival.
e local control was 99 % aer 12 months, 88 % aer 24 months and 75
% aer 60 months.
Conclusions: We could nd a good feasibility of a postoperative RT or
RCT for elderly patients with SCCHN. Especially the local control was
quite satisfactory. ere seems to be no obvious dierence in overall sur-
vival in comparison with other collectives of younger patients or unselect-
ed patients regarding age. Our results show, that a de-intensication of
treatment just because of age seems not to be justied.
Disclosure Statement: On behalf of all authors, the corresponding author declares
that there are no conicts of interest.
446
Improved Detection of Promising Epigenetic Biomarkers
for Head and Neck Cancer in Saliva
Juliane Priese 1; Anna-Bawany Hums 2; Theresa Erler 2; Lars Jansen 3;
Matthias Dürst 3; Martina Schmitz 2; Orlando Guntinas-Lichius 1;
Alfred Hansel 2
1HNO-Klinik, Universitätsklinikum Jena, Jena, Deutschland
2oncgnostics GmbH, Jena, Deutschland
3Klinik und Poliklinik für Frauenheilkunde und Fortpanzungsmedizin,
Funktionsbereich „Gynäkologische Molekularbiologie“, Universitätsklinikum
Jena, Jena, Deutschland
Purpose: Head and neck squamous cell carcinoma (HNSCC) is a het-
erogeneous disease. Two thirds of patients are diagnosed with advanced
tumour stages.1 erefore, we currently conduct a feasibility study with
the aim to prove that our validated cancer-specic markers, detected in
DNA from primary tumour tissue, may also be detectable in non-invasive
saliva samples.
Methods: HNSCC-specic DNA methylation markers (Z1-Z5; reference
ACTB) were validated using fresh-frozen tissue samples (20x HNSCC;
20x controls) by methylation-specic multiplex QPCR on the cobas z 480
analyzer (Roche). e aim is to include 200 patients in the study. For mul-
tiplex QPCR testing both, tissue and saliva are collected from each HN-
SCC patient at the Department of Otorhinolaryngology, Jena University
Hospital. Isolated genomic DNA is bisulte-converted before use.
Results: Validation of Z1 – Z5 by multiplex QPCR yielded 100% clinical
sensitivity and 95% specicity, if 1/5 markers were positive, in HNSCC
and control tissues. Single marker sensitivity ranged from 30% to 70%
and specicity from 95% to 100% in this validation sample set. In samples
collected from the rst six HNSCC patients, the markers Z1, Z3-Z5 were
detected in the six available tissue samples. Z1 showed matching results
between all six tissue and saliva samples. Z5 showed positive detection
in 6/6 tissue and 5/6 saliva samples. Z2 – Z4 had weak detection rates in
saliva samples so far. Results from the control group are not yet available.
Conclusions: Preliminary results support our study hypothesis to
robustly detect HNSCC markers in both, tissue and saliva. Utilization of
saliva samples for cancer-specic diagnostic assays based on epigenetic
markers will be useful in in vitro diagnostics aiming at secondary and
tertiary prevention.
Reference:
1. Gatta G, et al. Eur J Cancer 2015; 51(15):2130-2143
Disclosure Statement: is study was supported by oncgnostics GmbH; Jena;
Germany.
474
Eects of Decitabine on the Expression of Immune
Checkpoints Molecules (ICM)
Adrian Fehn 1; Jasmin Ezic 1; Cornelia Brunner 1; Sandra Jeske 1;
Lisa Puntigam 1; Johannes Döscher 2; Patrick J. Schuler 2;
Thomas K. Homann 2; Simon Laban 2
1HNO-Klinik der Universität Ulm, Forschungslabor, Ulm, Deutschland
2HNO-Klinik der Universität Ulm, Ulm, Deutschland
Purpose: Decitabine (DAC) reduces DNA methylation unspecically.
DNA demethylation increases the expression and repertoire of cancer-tes-
tis antigens (CTA) in cancer cells, potentially enhancing immunogenicity.
DAC eects on immune cell (IC) phenotype and function in the tumor
microenvironment need to be taken into consideration. To this end, we
set out to characterize DAC induced changes in IC.
Methods: Peripheral blood mononuclear cells (PBMC) of patients with
oropharyngeal carcinoma and healthy controls were cultivated and treat-
ed at 1µmol/l for 5 consecutive Days. Changes in ICM expression were
analyzed by ow cytometry. Four panels were designed with ve backbone
markers (CD3,4,8,39,19) each. Expression of ICMs (PD-1, CTLA4, BTLA,
CD137, CD27, GITR, LAG-3, OX40, TIM3, VISTA, ICOS, TIGIT) was
analyzed. Cytotoxicity was monitored with Annexin V / 7AAD staining
plus CD3,4,8,39&19.
Results: Variations in dierent immune cell populations’ susceptibility to
DAC’s cytotoxicity were observed. CD19+ B cells were depleted by 78%,
CD39+ cells were depleted by 29%, CD8+ cells increased by 19% and
CD4+ cells by 38% compared to control treated cells. DAC evokes a shi
in the expression pattern of immune checkpoint molecules: In healthy
controls DAC reduced the expression of PD1 and CTLA4 in CD4+ cells,
whereas tumor patients showed increased expression of these ICMs in
CD8+ and CD4+ cells. CD19+ cells show an increase in OX40 and de-
crease in CD27 expression. CD39+ cells show decreased levels of PD1,
CD137, CD27, ICOS and TIGIT.
Conclusions: DAC treatment alters the expression of ICM and lympho-
cyte subpopulations proportions. is needs to be considered when com-
bining DAC with immunotherapy. Further experiments are ongoing to
validate and extend our ndings.
Disclosure Statement: P.J.S.: Advisory Boards: BMS; MSD. T.K.H.: Advisory
Boards: MSD; BMS; MSD. Honoraria: Merck Serono; BMS. S.L.: Advisory Boards:
Merck Sharp & Dohme (MSD); Bristol Myers Squibb (BMS); Astra Zeneca (AZ).
Honoraria: MSD; BMS; AZ; Merck Serono. All other authors indicated no poten-
tial conict of interest.
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475
Cell-Free DNA in Plasma or Saliva for Minimally Invasive
Monitoring of Head and Neck Cancer Patients
Romina Roesch 1, 2; Irina Kerle 2; Markus Wirth 3, 4; Markus Nieberler 5;
Nicole Pfarr 6; Carolin Mogler 6; Fabian Stögbauer 6; Philipp Blüm 2;
Silvia Thoene 1, 4; Ramona Secci 1, 4; Andreas Bietenbeck 1; Sara Krippgans 5;
Jakob Rinecker 3; Christoph Straube 4, 7; Clemens Heiser 3;
Klaus Dietrich Wol 5; Wilko Weichert 4, 6; Stephanie Combs 4, 7;
Florian Bassermann 2, 4; Jürgen Ruland 1, 4; Christof Winter 1, 4
1Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der
Technischen Universität München , München, Deutschland
2III. Med. Klinik für Hämatologie und Onkologie, Klinikum rechts der Isar der
Technischen Universität München, München, Deutschland
3Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Klinikum rechts der
Isar der Technischen Universität München, München, Deutschland
4DKTK Partnerstandort München, Deutsches Krebsforschungszentrum (DKFZ)
Heidelberg
5Klinik und Poliklinik für Mund- Kiefer- Gesichtschirurgie, Klinikum rechts der
Isar der Technischen Universität München, München, Deutschland
6Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische
Universität München, München, Deutschland
7Klinik und Poliklinik für RadioOnkologie und Strahlentherapie, Klinikum rechts
der Isar der Technischen Universität München, München, Deutschland
Purpose: In patients with head and neck cancer (HNC), disease
monitoring and recurrence detection are currently based on clini-
cal examination and imaging. Liquid proling of tumor-derived nu-
cleic acids such as cell-free tumor DNA (ctDNA) in plasma and in sa-
liva could provide better monitoring and earlier recurrence detection.
Here, we aim is to determine to which extent ctDNA and HPV DNA can
be detected in plasma and saliva, and which sample material is more suit-
able for liquid-based HNC proling.
Methods: In 92 HNC patients, blood plasma and saliva samples were pro-
spectively collected aer surgery and analyzed with digital droplet PCR
(ddPCR) assays to detect two TERT promoter hotspot mutations. In the
subgroup of 50 patients with HPV-associated tumor localizations, cell-
free DNA (cfDNA) was tested for HPV16 (E7) in plasma and saliva. To
increase the detection rate, mutations in the primary tumor were iden-
tied with NGS (45 genes) and ctDNA was quantied using individually
designed mutation-specic ddPCR assays.
Results: In 33% (30/92), ctDNA was detected in plasma, in 38% al-
ready in early tumor stages (I/II). In saliva, ctDNA was detected in 52%
(17/33). In the course of disease, a tumor progression could be detect-
ed by increasing ctDNA concentrations in plasma or saliva on aver-
age 5 months (2 weeks to 13 months) earlier than by clinical imaging.
In p16-pos. patients (n=16), HPV16 cfDNA was detected in plasma in
39% (6/16), in 50% already in early tumor stages (I/II). P16-pos. HPV-
neg. patients (10/16) showed an unfavorable clinical course compared to
p16-pos. HPV-pos. patients (30% died, 79% had a relapse or progressive
disease).
Conclusions: Liquid proling with ddPCR-based detection of ctDNA
in blood and saliva is a promising tool for disease monitoring and early
recurrence detection in HNC patients. In HPV-associated tumors, HPV
cfDNA could be a complementary marker for disease monitoring and for
identifying a subgroup of p16-pos. tumors that are not driven by HPV
infection.
Disclosure Statement: no conict of interest
545
Intrathecal Ziconotide and Morphine Using Cervical Catheters
for Cancer Analgesia
Denis Dupoiron; Gabriel Carvajal; Francois Boré; Pierre Yves Dubois;
Damien Leblanc; Sabrina Jubier Hamon; Thierry Delorme;
Virginie Jaoul; Nathalie Lebrec
institut de cancérologie de l‘ouest , ANGERS, Frankreich
Purpose: Pain remains the rst symptom in cancer population at an ad-
vance stage of the disease (1). Intrathecal drug delivery systems (IDDS) is
ecient to relieve pain refractory to comprehensive medical management
(2). However, IDDS through cervical catheters with Ziconotide for Head
and Neck Cancer (HNC) pain is a new option never described on litera-
ture. is prospective follow up study was designed to evaluate results of
cervical IDDS with Ziconotide for Cancer pain at the ICO.
Methods: Patients were treated from 2010 to 2017, aer selection for
IDDS based on multidisciplinary meeting discussion. Aer a complete
withdrawal of systemic opioids, IDDS-treated patients were prescribed
a combined intrathecal regimen (morphine, ropivacaine and ziconotide)
through a catheter placed behind the cervical spinal cord. Post-implant
assessment of pain was determined using a numeric rating scale (NRS).
Results: 43 patients were included from 2010 to 2017, total therapy du-
ration accounts for 9013 IDDS-days. Implanted patients suered from
severe pain (mean presurgical NRS 8.6±0.8) despite a mean 566 +/-112
mg oral morphine equivalent daily dose. Median survival time aer IDDS
was 125 ± 176 days. IDDS provided great pain relief with signicant dif-
ference (p < 0.01) aer 1 week (2.4+/- 0,46), 1 month (2.7 +/- 0,44) and 2
months (2.8+/- 0.55) 50%. Only one serious adverse eect was observed
with ziconotide.
Conclusions: Long-term IDDS using a multidrug regimen including
ziconotide for HNC pain through cervical intrathecal catheters reduce
pain scores and seems safe in our study population, using mainly a percu-
taneous lumbar approach.
References:
1. van den Beuken: Update on Prevalence of Pain in Patients With Cancer -
JPSM. 2016;51(6)
2. Smith TJ: Randomized clinical trial of IDDS -JCO 2002;20(19)
Disclosure Statement: Dr Dupoiron is consultant for Medtronic and RIEMSER
Pharma GmbH.
595
Expression of the Immune Modulators of the PD-1: PD-L1 Axis
in oral Leukoplakia
Jutta Ries 1; Falk Wehrhan 1; Christoph Baran 1; Abbas Agaimy 2;
Eva Danzer 1; Stella Bolze 1; Maike Büttner-Herold 2; Marco Kesting 1;
Manuel Weber 1
1Mund-, Kiefer und Gesichtschirurgische Klinik, Unversitätsklinikum Erlangen,
Erlangen, Deutschland
2Pathologie, Unversitätsklinikum Erlangen, Erlangen, Deutschland
Purpose: PD/PD-L1 Immune Checkpoint overexpression is involved in
immunosuppression and the failure of an immune response against tumor
cells. Cancer immunotherapy using antibodies targeting this axis has be-
come a new therapeutic approach also for patients suering from OSCC.
Little is known about its expression in oral precancerous lesions like oral
leukoplakia (OLP). e aim of the study was to check whether altered PD/
PD-L1 expression already exists in OLP and whether it is associated with
malignant transformation.
Methods: PD-1 and PD-L1 expression were immunohistologically an-
alyzed separately in the epithelium and the subepithelium of OLP that
transformed malignant within 5 years (T-OLP), in OLP without malig-
nant transformation (N-OLP), in corresponding OSCC and in healthy
oral mucosa (NOM). Additionally, RT qPCR analysis for PD-L1 expres-
sion was done in the entire tissues. e expression rates were compared
and statistical signicance of the expression change between the groups
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and the association between overexpression and malignant transforma-
tion was determined.
Results: PD-1 was overexpressed in the epithelial and subepithelial com-
partment of T-OLP compared to N-OLP (PE=0.001; PS=0.005). No signif-
icant dierence in PD-L1 mRNA expression between transforming and
non-transforming OLP could be demonstrated (P=0.10). However, the
PD-L1 protein was signicantly overexpressed in the epithelial section of
transforming OLP (p=0.007), but not in the subepithelial compartment
(p=0.25) compared to N-OLP. Additionally, this overexpression was sig-
nicantly associated to malignant transformation within 5 years.
Conclusions: PD-1/PD-L1 may represent a prognostic indicator to deter-
mine the risk of malignant progression of OLP. Local immunosuppression
in the epithelium could be induced by PD-L1 overexpression in epithelial
cells and trigger malignant transformation. Hence, checkpoint inhibitors
could counteract tumor development and serve as therapeutic agents in
patients with high-risk OLP lesions.
600
Zoledronate Shifts Macrophage Polarization towards M1
in Vivo - An Animal Study on Wistar Rats
Manuel Weber 1; Kerstin Amann 2; Andi Homm 3; Stefan Müller 3; Jutta Ries 1;
Carol Geppert 4; Raimund Preidl 1; Marco Kesting 1; Falk Wehrhan 1
1Mund-, Kiefer- und Gesichtschirurgische Klinik Erlangen, Erlangen,
Deutschland
2Pathologisches Institut, Nephropathologische Abteilung, Erlangen,
Deutschland
3Erlangen, Mund-, Kiefer- und Gesichtschirurgische Klinik, Erlangen,
Deutschland
4Pathologisches Institut, Erlangen, Deutschland
Purpose: Clinical studies and in vitro analyses indicate that immunomod-
ulatory properties of bisphosphonates contribute to the development of
medication associated osteonecrosis of the jaw (MRONJ) as well as to the
anti-metastatic eect observed in certain groups of breast cancer patients.
Macrophages are precursor cells of osteoclasts and could be potential can-
didates for the mediation of immunological eects of bisphosphonates.
Aim of the study was to investigate the inuence of zoledronate on density
and polarization of macrophages in dierent tissues of the Wistar rat.
Methods: A total of 120 animals (6-month-old male Wistar rats) were
divided into 4 groups, 56 of which were treated with 8x 40mg/kg body
weight zoledronate i.p. Aer 2, 4 and 8 weeks the tissues skin, lung, spleen
and tongue were removed and immunohistochemically examined for the
expression of CD68, CD163 and iNOS positive cells using a tissue mi-
croarray.
Results: In bisphosphonate treated animals a signicantly increased mac-
rophage cell count (increased CD68 expression) as well as signicantly
increased iNOS expression and signicantly decreased CD163 expression
was observed.
Conclusions: Bisphosphonate application leads to a shi of macrophage
polarization towards M1 in vivo. is provides a possible explanation for
the clinically observed anti-tumor eect of bisphosphonates.
Disclosure Statement: e authors declare no conict of interest.
632
A Randomized Phase II Study on the Optimization of
Immunotherapy in Squamous Carcinoma of the Head and
Neck (SCCHN) – OPTiM (AIO-KHT-0117)
Viktor Grünwald 1; Dennis Hahn 2; Jürgen Alt 3; Justin Hasenkamp 4;
Konrad Klinghammer 5; Gunter Schuch 6; Gunnar Hapke 7; Philipp Ivanyi 8
1Universitätsklinikum Essen, Innere Klinik, Essen, Deutschland
2Klinikum Stuttgart, Klinik für Hämatologie, Onkologie und Palliativmedizin,
Stuttgart, Deutschland
3Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III.
Medizinische Klinik und Poliklinik, Mainz, Deutschland
4Universitätsmedizin Göttingen, Georg-August-Universität, Hämatologie und
Onkologie, Göttingen, Deutschland
5Charité Universitätsmedizin Berlin Campus Benjamin Franklin, Medizinische
Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie,
Berlin, Deutschland
6HOPA - Hämatologisch-Onkologische Praxis Altona, Hamburg, Deutschland
7Kath. Marienkrankenhaus Hamburg gGmbH, Hamburg, Deutschland
8Medizinische Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie,
Onkologie und Stammzelltransplantation, Hannover, Deutschland
Purpose: e OPTIM trial investigates whether dual checkpoint block-
ade is superior to docetaxel chemotherapy as early salvage therapy in re-
current or metastatic SCCHN (R/M-SCCHN). e primary endpoint is
overall response rate aer randomization, hypothesizing that dual check-
point blockade improves ORR to 25% compared to 10% with docetaxel.
Secondary endpoints are overall survival, progression-free survival, safety,
and quality of life.
Methods: 280 patients with R/M-SCCHN progressing aer plati-
num-based chemotherapy or within 6 months aer RCT will initially re-
ceive nivolumab monotherapy (240 mg Q2W). ey are closely followed
for tumor progression by radiologic assessment at increased frequency
(i.e. every 4-6 weeks). Patients who progress during the rst 24 weeks of
nivolumab monotherapy are randomized 1:1 between intensied immu-
notherapy (nivolumab 3 mg/kg Q2W + ipilimumab 1 mg/kg Q6W) and
chemotherapy (docetaxel 75 mg/m2 Q3W). 154 patients are planned to
be randomized. Patients who do not progress continue nivolumab mono-
therapy according to standard of care. Aer randomization, study treat-
ment continues until disease progress or for up to 12 months.
Results: Recruitment started in July 2018 and is ongoing. Results will be
published aer nalization of study.
Disclosure Statement: All authors have no relevant nancial or nonnancial
relationships to disclose.
OPTIM (EudraCT 2017-003349-14) study sponsor is AIO-Studien-gGmbH;
Berlin. e study is nancially supported by Bristol-Myers Squibb.
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Health Economy/Public Health
Vorträge
421
Health Economic Eects of Biosimilars: The Potential for the
Long-Term Financing of Oncological Care and Therapeutic
Innovations
Michael Patrick Lux 1; Florian Kron 2, 3; Kai Hübel 2
1Kooperatives Brustzentrum Paderborn, Klinik für Gynäkologie und
Geburtshilfe, Frauen- und Kinderklinik St. Louise, Paderborn, Deutschland
2University of Cologne, Faculty of Medicine and University Hospital of Cologne,
Dept. I of Internal Medicine, Köln, Deutschland
3FOM University of Applied Sciences, Essen, Deutschland
Purpose: Several new options for individualized and targeted therapies
in oncology and immunology are available or in development. However,
these are cost intensive, in particular in view of healthcare systems with
limited resources. Hence, new nancing approaches are warranted. Bio-
similars are biological drugs containing the active substance of an already
approved reference biological drug. e introduction of biosimilars can
relieve the burden on healthcare and thus nance new therapies. How-
ever, existing data shows that the saving potential in Germany is far from
exhausted.
Methods: Based on available health economic analyses, the actual use and
eects of biosimilars were determined using the examples of trastuzumab,
rituximab and G-CSF. e associated costs of the originator and biosimi-
lar were compared to determine the saving potential in the real world for
the German healthcare system. Incidence calculations were based e.g. on
data from the Robert-Koch-Institution, Munich cancer registry, quality
indicators of the certied centers and calculations of the IQWiG benet
assessments. Cost calculation was based on Lauer tax (15/12/2018).
Results: According to the example of trastuzumab and calculations based
on various sources, the number of patients with HER2-positive breast
cancer receiving trastuzumab in the adjuvant and metastatic setting
ranges from 8,199 to 14,380 and 4,643 to 4,670 cases/year, respectively.
is corresponds to a range of 118,745 to 208,250 cycles/year in the ad-
juvant setting and 236,793 to 238,170 cycles/year in the metastatic set-
ting. e annual saving potential would amount from 87,883,705 EUR to
120,496,027 EUR if all patients received the least expensive trastuzumab
biosimilar compared to the original drug.
Conclusions: e available data show that potential savings are far from
exhausted and that, if the option of biosimilars is fully exploited, enor-
mous resources can be released in the healthcare system in order to oset
nancing new innovative forms of therapy. Additional calculations for rit-
uximab and G-CSF will be provided.
Poster
57
Assessment of Metastatic Colorectal Cancer Patient
Preferences for Biologic Treatments in Germany Using a
Discrete Choice Experiment – Study in Progress
Moushmi Singh 1; Robert Bartsch 2, 2; Anna-Maria Stegherr 3;
Fränce Hardtstock 4; Margit Hemetsberger 5; Andrea Lebioda 2
1Health Economics, Amgen Ltd., Uxbridge, United Kingdom
2Value, Access & Policy, Amgen GmbH, Munich, Deutschland
3Medical Aairs, Amgen GmbH, Munich, Deutschland
4Ingress-Health HMW GmbH, Wismar, Deutschland
5Hemetsberger medical services, Wien, Österreich
Purpose: is is an ongoing discrete choice experiment (DCE) that aims
at understanding patient preferences in the systemic biologic treatment of
metastatic colorectal cancer (mCRC), focusing on the perception of ad-
verse event risk relative to the expected treatment benets.
Methods: is ongoing multicenter cross-sectional study is a based on
patient interviews using a DCE framework. It aims to include 150 patients
with mCRC from 15-20 sites in Germany. It includes adult patients (≥18
years) with a physician-reported diagnosis of mCRC actively or previous-
ly (within the previous 3 months) receiving or about to be initiated on a
rst-line mCRC therapy. All participants must provide written informed
consent. Patients are asked to make several stated (hypothetical) choices
in deciding between two alternative treatment options to quantify their
preferences for dierent mCRC treatment attributes, specically attri-
butes related to ecacy (e.g., overall survival) in relation to safety (e.g.,
risk of rash, infusion reactions, or gastrointestinal hemorrhage).
Results: is study is currently recruiting patients and results are expected
in December 2019. In a conditional logit regression model, the inuence
of dierent attribute levels on the probability of a patient’s choice for or
against a specic treatment alternative will be estimated. In an additional
analysis, utility values will demonstrate marginal willingness to accept a
given attribute if a specic treatment with a more favorable attribute level
could be received. Furthermore, relative importance of each attribute for
the overall decision for or against an option in the DCE will be provided.
Additionally, a latent class analysis to identify and describe patient sub-
groups will be done.
Conclusions: ere is a lack of research focusing on patient preferences
with a biological mCRC treatment and there are no existing data for Ger-
many so far. erefore, this study will facilitate a better understanding of
trade-os related to the existing treatment of the disease from the per-
spective of the German population.
82
Development of a Telemedical Software for the Organisation
of Oncological Councils and Tumor Conferences within the
Project “Tumornetzwerk Sachsen“
Sonja Hiemer 1; Sybil David 2; Axel Petzka 2; Nicole Lakowa 2
1Tumornetzwerk Sachsen/Onkologisches Zentrum St. Georg, Klinikum St. Georg
Leipzig, Leipzig, Deutschland
2Tumornetzwerk Sachsen, Klinikum St. Georg Leipzig, Leipzig, Deutschland
Purpose: Strategies for Cancer patients need to be discussed within in-
terdisciplinary tumor conferences. e development of the soware “eTu-
morkonsil” for telemedical consultation of oncological patients will allow
physicians of various disciplines and medical facilities to network digitally
wherever located. is will improve the medical care of cancer patients,
also for patients in structurally weak areas.
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Methods: e application “eTumorkonsil” is going to be developed on an
established telemedicine platform and will allow physicians to share onco-
logical councils using electronical (e-) councils or to take part in e-tumor
conferences, two possible functions within the soware. Furthermore, all
clinical information will be made available directly to a digital patient re-
cord. e user of the application, dened by a login, may request second
opinions on oncological issues and discuss patients digitally using a high
quality phone and video conferencing system. e program is web based
and therefore capable of running independent and free of any connection
into operating systems.
Results: Uniform processes ensure a fast procedure of the digital councils
without media disruption. e transmitted patient data is encrypted in
agreement with the data protection requirements. e application is user
friendly, so that the preparation and follow-up as well as the execution
of the tumor conference are logically organized. erapy recommenda-
tions are provided on the platform by standardized digital paths within
24 hours.
Conclusions: In the Free State of Saxony physicians who are responsible
for outpatient and inpatient treatment are able to be networked with the
telemedical application “eTumorkonsil” in a multidirectional way. Hereby
it is possible to optimize the care of cancer patients; especially in structur-
ally weak regions; by connecting them to certied cancer centers. „eTu-
morkonsil“ oers an innovative and time-ecient support in oncological
care for everyday medical practice and stand for a continuous quality as-
surance in the context of patient care.
230
Measuring Utilities in Cancer Patients - The EORTC QLU C10D
Matthias Büttner 1; Eva Gamper 2; Georg Kemmler 2
1Universitätsmedizin Mainz, Institut für Medizinische Biometrie, Epidemiologie
und Informatik, Mainz, Deutschland
2Medizinische Universität Innsbruck, Department für Psychiatrie und
Psychotherapie, Innsbruck, Österreich
Purpose: Health economic analysis and therefore cost-utility studies are
becoming more prominent in cancer research. Generic utility instruments
may not address cancer patients in a suitable way due to the complexity
of the disease [1]. e EORTC QLU C-10D is a new multi-attribute utility
instrument derived from the cancer-specic EORTC QLQ C-30, which
is one of the most widely-used quality of life instruments for assessing
cancer patients’ quality of life. e aim of this project was to develop can-
cer-specic utility weights derived from the EORTC QLQ C-30 for ve
European countries.
Methods: A professional marketing company set up the DCEs with a gen-
eral population of 1000 participants in each country. Discrete Choice Ex-
periments (DCEs) from a general population in ve European countries
(Austria, Germany, France, Italy and Poland) were used to derive utilities
from the C-30. e key dimensions used for the discrete choice experi-
ments have been identied in previous studies.
Results: e dimension that impacted most on choice was physical func-
tioning followed by pain for all ve European countries. Regarding the or-
der of impact for the other dimensions, slight variations were seen across
the countries. Relevant cancer-related symptoms with a moderate eect
were nausea and bowel problems. A small impact across all ve European
countries was seen for fatigue, sleep problems, and appetite loss. e high-
est utilities were seen for Italy, while the lowest were obtained for France.
Conclusions: is project provided the rst country-specic European
utility weights for the QLU C-10D in ve EU countries. ese utilities can
be applied in future clinical trials using the EORTC QLQ C-30. Further
valuations for European and Asian countries are performed.
Reference:
1. Pickard AS, Ray S, Ganguli A, Cella D. Comparison of FACT- and EQ-5D-ba-
sed utility scores in cancer. Value Health. 2012;15(2):305-11.
Disclosure Statement: e authors have nothing to disclose.
751
Time-Dependent Risk Predictions As Novel Method
to Improve Screening Eciency
Vinzenz Völkel 1, 2; Teresa Draeger 1, 2; Sabine Siesling 3; Hendrik Kojberg 3
1Caritas Krankenhaus St. Josef, Regensburg, Deutschland
2Tumorzentrum Regensburg, Regensburg, Deutschland
3Universität Twente, HTSR, Enschede, Niederlande
Purpose: Risk-prediction tools allow to classify patients into risk-groups
based on risk thresholds. e usage of information concerning an indi-
vidual’s risk development over time would facilitate further tailoring of
screening schemes.
Methods: In a simulation analysis, three screening approaches (risk-
based, time-independent: cumulative approach CA; risk-based, time-de-
pendent: cumulative approach with interval-specic reevaluation CAIR,
interval-specic approach ISA) are compared regarding their impact on
screening-eciency. For this purpose, 81 scenarios featuring 5,000 pa-
tients with time-dependent risk estimations for a hypothetical disease D
and ve consecutive intervals of one year are simulated, using dierent
parameters to model disease progression, risk-distribution, risk-correla-
tion, and target detection rate of screening (tdr). e results of these sim-
ulation analyses are validated using a real-world clinical case-study based
on German breast cancer patients and the INFLUENCE-nomogram for
locoregional breast cancer recurrence.
Results: If individual, time-dependent risk estimations were used to per-
sonalize screening at a xed tdr of 90%, the percentage of saved screen-
ing examinations relative to an uninformed approach could exceed 20%,
depending on the simulated scenario. Whereas the time-independent
approach CA is associated with acceptable saving potentials in case of a
relatively homogenous risk distribution, the time-dependent approaches
CAIR and ISA are superior when risk-variation increases. With slowly
progressing diseases, approach CAIR yields the highest eciency on pop-
ulation level, for rapidly progressing diseases, approach ISA is superior.
e possible benets of time-dependent risk-based screening were con-
rmed in the real-world clinical case-study.
Conclusions: An appropriate usage of time-dependent risk-predictions
may considerably enhance screening eciency. erefore; predicting risk
development over time should be incorporated in future prediction-tools
and decision-algorithms.
771
Gera: a Health Economic Trial to Analyze the Impact of eHealth
in Breast Cancer Care
Tanja Eggersmann 1; Christoph Riese 2; Claudia Wenzel 2; Timo Schinköthe 2;
Tom Degenhardt 1; Rachel Würstlein 1; Nadia Harbeck 1; Manfred Welslau 3
1Breast Center, University Hospital Munich, Department of Gynecology and
Obstetrics, CCC of LMU, München, Deutschland
2CANKADO, Kirchheim bei München, Deutschland
3Hematological-Oncological Practice, Hospital Aschaenburg, Aschaenburg,
Deutschland
Purpose: In breast oncology, the increasing number of oral drug therapies
poses great challenges for patient management. Numerous studies
demonstrate that well-informed patients develop higher condence
in their treatment and a greater sense of disease control, resulting in
increased adherence and persistence as well as potentially better outcome.
e electronic Patient Reported Outcome (ePRO) tool CANKADO is
designed to help oncologists to bridge the gap between good, personalized
care and a time and resource-saving treatment for cancer patients.
Methods: Aim of GERA is to assess the economic impact of an ePRO tool
in breast cancer care. It is a prospective, single arm, non-interventional
trial, based on questionnaires that answered by patients via the CAN-
KADO Patient App. All patients undergoing systemic therapy for breast
cancer with access to CANKADO will be included in the evaluation. is
study will take place in 10 German centers and 337 patients will be includ-
ed in the study. e enrollment phase of patients will last 6 months, while
the individual patient observation and accompaniment phase through
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CANKADO will continue for 3 months. Primary objective is to gain
knowledge on the health economic impact of CANKADO resource uti-
lization in breast cancer care including the evaluation of physicians’ time
and patient experience. As secondary objectives, exploratory analysis of
all collected information is planned. is includes the socio-demograph-
ic patient information, clinical characteristics, quality-of life and patient
documentation behavior.
Results: e GERA trial is ongoing. Results will be presented at the con-
ference.
References:
1. Eggersmann TK, Harbeck N, Schinkoethe T, Riese C. eHealth solutions for
therapy management in oncology. Breast Cancer Management vol.6, no.3,
special report (2018), Future medicine. https://doi.org/10.2217/bmt-2017-0005
2. Schinkothe T. Individualized eHealth Support for Oncological erapy Ma-
nagement. Breast care (Basel, Switzerland), 2019;14:130-4.
Disclosure Statement: None declared
Imaging
Poster
288
A Deep Learning-Based Pipeline for The Automation of the
HER2 Gene Amplication Status Detection on Digitalized
Whole Fluorescence in Situ Hybridization (Fish) Slides in
Breast and Gastric Cancer
Falk Zakrzewski 1; Sarah Schmell 1; Walter De Back 2; Martin Weigert 3, 4;
Torsten Wenke 5; Silke Zeugner 1; Robert Mantey 6; Christian Sperling 1;
Ingo Röder 2, 6; Daniela Aust 1, 6; Pia Hönscheid 1, 6; Gustavo Baretton 1, 6
1Institut für Pathologie des Universitätsklinikums Carl Gustav Carus, Dresden,
Deutschland
2Technische Universität Dresden, Dresden, Deutschland
3Center for Systems Biology Dresden, Dresden, Deutschland
4Max-Planck-Institut für molekulare Zellbiologie und Genetik, Dresden,
Deutschland
5ASGEN GmbH & Co. KG, Dresden, Deutschland
6Nationales Centrum für Tumorerkrankungen (NCT) Dresden, Dresden,
Deutschland
Purpose: e human epidermal growth factor receptor 2 (HER2) gene
amplication status is important for therapy assessment in breast and gas-
tric cancer. It is visually assessed by pathologists based on FISH imaging
using a uorescence microscope or uorescence scanner. To automatize
this daily clinical routine in terms of speed, accuracy and objectivity, a
multi-step deep learning (DL) based pipeline was developed to mimic the
evaluation steps performed by pathologists.
Methods: e DL pipeline relies on (1) the prediction of the image-wide
HER2 gene amplication status via image classier convolutional neural
networks (CNNs), (2) the detection, localization and classication of in-
terphase nuclei and their HER 2 and CEN17 uorescence signals based on
(2a) object detection and (2b) pixel-wise segmentation networks and (3)
the visualization of the decision making of the networks to enable inter-
pretability by pathologists.
Results: We demonstrate that the accuracy of our DL pipeline is on par
with a team of pathologists for the classication of whole FISH slides.
Moreover, by classifying each nucleus independently by dierent net-
works, our system provides deep medical reports increasing both robust-
ness and interpretability.
Conclusions: Our pipeline is a large step in automating the evaluation of
the HER2 status of tumors using whole FISH slide scans and in optimiz-
ing the documentation of each tumor sample by automatically annotating
and reporting of the HER2 gene amplication status. is system is in
principle also transferable to all current FISH-based analyses which are
routinely performed at pathology institutes.
Disclosure Statement: Falk Zakrzewski, Martin Weigert and Torsten Wenke are
founders of the startup company ASGEN.
519
Sodium MRI at 7 Tesla as a Potential Biomarker for Tumor
Inltration and IDH Status in Glioma Patients
Sebastian Regnery 1, 2; Nicolas Behl 3; Tanja Platt 4; Nina Weinfurtner 5;
Katerina Deike-Hofmann 5; Felix Sahm 6, 7; Mark E. Ladd 4, 8;
Heinz-Peter Schlemmer 5; Jürgen Debus 1, 2; Stefan Rieken 1, 2;
Daniel Paech 5; Sebastian Adeberg 1, 2
1Heidelberg University Hospital, Department of Radiation Oncology,
Heidelberg, Deutschland
2German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation
Oncology, Heidelberg, Deutschland
3Siemens Healthineers, Erlangen, Deutschland
4German Cancer Research Center (DKFZ), Division of Medical Physics in
Radiology, Heidelberg
5German Cancer Research Center (DKFZ), Division of Radiology, Heidelberg
6Heidelberg University Hospital, Department of Neuropathology, Heidelberg
7German Cancer Research Center (DKFZ), Clinical Cooperation Unit
Neuropathology, Heidelberg
8University of Heidelberg, Faculty of Physics and Astronomy and Faculty of
Medicine, Heidelberg
Purpose: ese are the rst data from a prospective trial investigating so-
dium (23Na) MRI at 7 Tesla (T) as a potential biomarker for tumor inltra-
tion and isocitrate dehydrogenase (IDH) mutation.
Methods: 30 glioma patients underwent 23Na MRI on a 7 T scanner (Sie-
mens Healthineers, Erlangen, Germany) parallel to standard 3T MRI
before chemoradiation. A self-developed density-adapted 3D radial pro-
jection pulse sequence [1] with consecutive iterative 3D-DLCS recon-
struction [2] was employed. Areas of gadolinium contrast enhancement
(gdce), non-enhancing T2 hyperintensity (regarded as edema) as well
as necrosis were segmented, and regions of interest were placed inside
normal-appearing white matter (nawm) on 3T MRI. All segmentations
were registered to the 23Na images in MITK (http://mitk.org). e median
23Na signal of all areas was compared by pairwise t-tests, and the dier-
ence in median 23Na signal of the whole tumor was compared between
IDH-mutated (mut, N=6) and IDH-wild-type (wt, N=18) gliomas by a
Mann-Whitney U test.
Results: e 23Na signal increased successively from nawm to necro-
sis (mean ± sd [mM]: nawm = 37.8 ± 5.9, edema = 54.7 ± 10.6, gdce =
61.7 ± 13, necrosis = 81.9 ± 17.5) and the signal dierences between all
areas proved signicant (p-values for all pairwise comparisons < 0.01).
Furthermore, IDH-mut gliomas showed signicantly higher 23Na signal
than IDH-wt gliomas (median (interquartile range) [mM]: wt = 52.4 (46
– 58.6), mut = 65 (58.9-67.1), p = 0.0094).
Conclusions: e continuous gradient of 23Na signal from central necro-
sis to white matter suggests a correlation with tumor inltration. Consid-
ering the additional correlation with IDH status, 23Na MRI could enhance
identication of biopsy sites and assist image-guided surgery and radio-
therapy.
References:
1. Nagel et al., e potential of relaxation-weighted sodium magnetic resonance
imaging as demonstrated on brain tumors. 2011.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts104
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2018
2. Behl et al., ree-dimensional dictionary-learning reconstruction of (23)Na
MRI data. 2016.
Disclosure Statement: N.G.R.B. currently works for Siemens Healthineers.
641
Development of a Convolutional Neural Network (CNN)-Based
Classier for Automated Tissue and Tumor Annotation of
Matrix-Assisted Laser Desorption/Ionization (MALDI) Data
Falk Zakrzewski 1; Linna Sommer 1; Christian Sperling 1; Annelie Zürich 1;
Walter De Back 2; Nico Scherf 2; Ingo Röder 2, 3; Daniela Aust 1, 3;
Pia Hönscheid 1, 3; Gustavo Baretton 1, 3
1Institut für Pathologie des Universitätsklinikums Carl Gustav Carus, Dresden,
Deutschland
2Technische Universität Dresden, Dresden, Deutschland
3Nationales Centrum für Tumorerkrankungen (NCT) Dresden, Dresden,
Deutschland
Purpose: Proteins and peptides represent the phenotype of the tumor at
the time of treatment. Consequently, the tumor proteome is a promising
target to dene novel biomarkers. MALDI combines the identication of
the proteome by means of mass spectra according to time-of-ight masses
(m/z), and the macroscopic anatomy of the tissue compartments. Deep
Learning is largely suitable for addressing the complex MALDI data for
automation of tumor classication by identication of tumor-specic pep-
tide features. erefore, a complementation of MALDI with Deep Learn-
ing pipelines will largely bring forward automated pathological tumor
slide analysis.
Methods: Regions of interest (ROI) of human cancer tissue slides are de-
ned by pathologists and are translated into mass spectra patterns used
for protein/peptide composition and quantication by MALDI. e data
is then transferred into Convolutional Neural Networks (CNNs) for ex-
tracting ROI-specic features. ese trained CNNs are subsequently ap-
plied for autonomous prediction of the tumor content and tumor tissue
localization in previously uncharacterized tissue slides from tumor sam-
ples on the basis of their MALDI spectra.
Results: Trained CNNs can be used to automatically classify, quantify
and mark tumor regions in MALDI imaging data. Morphologically in-
distinguishable tumors can be subdivided and analyzed regarding their
molecule-dependent heterogeneity at a very high resolution (down to 5x5
micrometer).
Conclusions: Our mission is to oer MALDI imaging as a diagnostic
complement for immunohistochemically analysis. We will provide our
MALDI pipeline as a broad application in CNN-based automated tumor
diagnostics and cancer research projects to enable the identication of
new protein/peptide biomarkers.
Leukemia, Myelodysplasia, Transplantation
Best-of-Abstracts-Vorträge
420
Nilotinib (NIL) vs. NIL Plus Pegylated Interferon alpha2B (IFN)
Induction and NIL or IFN Maintenance Therapy for Newly
Diagnosed BCR-ABL1+ Chronic Myeloid Leukemia (CML)
Patients (PTS) in Chronic Phase
Thomas Ernst 1; Susanne Saußele 2; Andreas Burchert 3;
Gabriela Maria Baerlocher 4; Tim Henrik Brümmendorf 5;
Paul Graf La Rosée 6; Dominik Heim 7; Stefan W Krause 8;
Philipp Le Coutre 9; Dietger Niederwieser 10; Thoralf Lange 11;
Mathias Hänel 12; Frank Stegelmann 13; Kirsi Manz 14;
Danny Himsel 1; Rüdiger Hehlmann 15; Christian Fabisch 1;
Markus Prrmann 14; Andreas Hochhaus 1
1Klinik für Innere Medizin II (Hämatologie/Onkologie), Universitätsklinikum
Jena, Jena, Deutschland
2Universitätsmedizin Mannheim
3Philipps Universität Marburg
4Inselspital Bern
5Uniklinik RWTH Aachen
6Schwarzwald-Baar Klinikum, Villingen-Schwenningen
7University Hospital Basel
8Universitätsklinikum Erlangen
9Charité - Universitätsmedizin Berlin
10University of Leipzig
11Asklepios Klinikum Weissenfels
12Klinikum Chemnitz
13University Hospital of Ulm
14IBE Ludwig-Maximilians-Universität München
15ELN-Foundation
Purpose: e TIGER-study (NCT01657604) is a multicenter, randomized
phase III trial to evaluate ecacy an d to lerability of NIL 2*300mg/d
monotherapy vs NIL 2*300mg/d + IFN and the option to discontinue
therapy aer IFN maintenance as rst line th erapy fo r ch ronic ph ase
CML pts.
Methods: 717 pts (429 male; median age 50.3 yrs, range 18-85) were re-
cruited from 109 sites in Germany, Switzerland, and the Czech Republic.
692 pts were randomized to receive NIL monotherapy (n=353) or NIL/
IFN combination therapy (n=339). Median observation time was 41 mo.
477 pts concluded the induction phase (conrmed major molecular re-
sponse, MMR, BCR-ABL1 <0.1% IS, aer >2 yrs of therapy) and reached
the maintenance phase of the study (NIL vs IFN monotherapy). 199 pts
achieved and maintained MR4 (BCR-ABL1 <0.01% IS) for at least one year
and discontinued all therapy.
Results: IFN signicantly improved rates of MR4 and MR4.5 (BCR-ABL1
<0.0032% IS). Median time to MMR was 5.4 vs 5.7 mo, to MR4 12.5 vs
20.9 mo and to MR4.5 23.2 vs 33.8 mo for NIL vs NIL/IFN, respectively.
From 199 pts who discontinued all therapy (MR4 for at least one year) 63
showed a molecular relapse (BCR-ABL1 >0.1%). Relapse free survival by
18 mo aer treatment discontinuation was 61% in the total cohort. 15 pts
(2.1%) progressed to advanced disease; 22 pts (3.1%) received allogeneic
stem cell transplantations.
Conclusions: is per protocol interim analysis demonstrates feasibili-
ty of 1st-line treatment with NIL combined with IFN. High rates of early
molecular responses indicate an option of treatment-free remission. e
addition of IFN to NIL signicantly improved rates of deep molecular re-
sponse (MR4 and MR4.5) at 12 and 18 mo of therapy.
Disclosure Statement: none
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2018
Poster
111
Selective Dependency of MLL-Rearranged Leukemia
on Immunoproteasome Function
Jonas Tönsing 1; Nuria Tubío Santamaría 1, 2; Tina Schnöder 1, 2;
Ulrike Seifert 3; Clemens Cammann 3; Juliane Mohr 1, 4;
Aniruddha Deshpande 5; Joanna Kirkpatrick 2; Alessandro Ori 2;
Florian Perner 6; Florian Heidel 1, 2
1Klinik für Innere Medizin II - Hämatologie und Internistische Onkologie, Jena,
Deutschland
2Leibniz-Institut für Alternsforschung - Fritz-Lipmann- Institut e.V., Jena,
Deutschland
3Friedrich Loeer Institut für Medizinische Mikrobiologie, Greifswald,
Deutschland
4Universitätsklinikum Magdeburg, Institut für Molekulare und Klinische
Immunologie, Magdeburg, Deutschland
5Sanford Burnham Prebys Medical Discovery Institute, Tumor Initiation and
Maintenance Program, National Cancer Institute-Designated Cancer Center,
San Diego, United States
6Dana-Farber Cancer Institute, Department of Pediatric Oncology, Boston,
United States
Purpose: Several pathways control the balance between self-renewal and
dierentiation to maintain leukemia stem cell (LSC) function. To iden-
tify dependencies of oncogenic fusion proteins, we performed global
proteome proling using MLL-AF9 (MA9) or AML1-ETO9a (AE) mu-
rine cells. In MLL-rearranged (MLLr) cells, GSEA revealed enrichment
of pathways related to proteasome function. is enrichment is present
in MLLr-leukemia but not in AE-LSCs. at may indicate an oncogene
specic vulnerability. In published AML datasets, immunoproteasome
(IP) subunits showed higher expression in MLLr compared to non-MLLr-
AML. IP is a proteasome variant constitutively expressed in hematopoietic
cells. It is relevant for mediating stress-responses during inammation.
Methods: To assess for functional dependency of MLLr cells on IP sub-
units we performed a CRISPR/Cas9 dropout screen in MLLr MOLM13
cells. Inactivation of LMP7 (IP subunit) resulted in outcompetition with
3/5 sgRNAs. Specicity of this nding was conrmed in 5 dierent cell
lines by RNAi using 2 shRNAs against LMP7. To conrm these ndings in
primary cells, we used a previously published conventional LMP7 knock-
out mouse model.
Results: LSK cells of LMP7 ko and wildtype mice were retrovirally in-
fected with either MA9 or NUP98-HOXA9 (non-MLLr control) to as-
sess for disease development by serial plating in methylcellulose. Only in
MA9 cells LMP7-deciency limited re-plating capacity. When we injected
MA9-infected LSK cells into recipient mice, recipients of MA9-LMP7-/-
cells and MA9-LMP7+/+ showed development of AML. However, recip-
ients of MA9-LMP7-/- cells had a signicant delay in AML development.
Conclusions: Taken together, our studies uncover a selective dependency
of MLLr-leukemia on IP function and identify LMP7 as a tractable target.
References:
1. Ebstein et al., “Emerging roles of immunoproteasomes beyond MHC class I
antigen processing, Cell Stem Cell, 2012.
2. García-Prat et al., “Proteostatic and Metabolic Control of Stemness, Cell Stem
Cell, 2017.
Disclosure Statement: Nothing to disclose.
214
Cytoreductive Treatment in ‘Real Life’ – Analysis of 434
Polycythemia Vera Patients in Germany
Carl Crodel 1; Kathleen Jentsch-Ullrich 2; Lutz Jacobasch 3; Philipp Kiewe 4;
Jens Kisro 5; Jörg Lipke 6; Siegfried Prenninger 7; Marcel Reiser 8;
Regine Wunschel 9; Andreas Hochhaus 1; Florian Heidel 1
1Jena, Klinik für Hämatologie und Onkologie, Universitätsklinikum Jena, Jena,
Deutschland
2Magdeburg, Gemeinschaftspraxis Hämatologie und Onkologie, Magdeburg,
Deutschland
3Dresden, Gemeinschaftspraxis Hämatologie und Onkologie, Dresden,
Deutschland
4Berlin, Onkologischer Schwerpunkt am Oskar-Helene-Heim, Berlin,
Deutschland
5Lübeck, Lübecker Onkologische Schwerpunktpraxis, Lübeck, Deutschland
6Dortmund, Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund,
Deutschland
7Passau, Onkologische Praxis, Passau, Deutschland
8Köln, Praxis Internistischer Onkologie und Hämatologie, Köln, Deutschland
9Nürnberg, Novartis Inc., Nürnberg, Deutschland
Purpose: e aim is to evaluate the use of phlebotomy and cytoreductive
therapy in patients with polycythemia vera.
Methods: For this analysis 11 centers provided data on 434 patients - 211
(48.6%) male and 223 (51.4%) female.
Results: Most patients were of older age (mean 71.4 years; 62.7 years at
diagnosis and 63,4% over 60 years).
100 patients (23.0%) had thromboembolic complications at time of diag-
nosis and 61 (14.1%) during treatment. Cardiovascular (CV) risk-factors
were reported for 320 patients (73.7%). Hypertension (86.9%) was the
most prevalent CV risk factor, followed by hypercholesteremia (18.8%),
diabetes mellitus (16.2%) and smoking (15.9%).
Phlebotomy was primary therapy in 301 patients (69.4%). Triggers to
start pharmacologic cytoreduction included the presence of high-risk
criteria (53.2%) and insucient disease control (22.6%). Asymptomatic
iron deciency (5.6%), symptomatic iron deciency (9.3%) and intoler-
ance to phlebotomy (5.3%) contributed to the limitation of phlebotomy
treatment.
Cytoreductive agents included hydroxycarbamide (n=320; 73.3%),
JAK-inhibitors (n=80; 18.4%), Interferon alpha (n=15; 3,5%), IMIDEs
(n=2; 0.5%) and other cytoreductive agents (n=6; 1.4%). While 11 patients
(2.5%) required combination, 137 (31.3%) patients had a persistent need
for phlebotomy.
Conclusions: Age was main factor for the majority of patients being cat-
egorized as ‘high risk. Although the majority of patients (>60%) present-
ed as ‘high risk’ according to international guidelines, 69.4% of patients
received phlebotomy as primary therapeutic approach. e low number
of primary cytoreductive treatment and occurrence of symptomatic iron
deciency and of intolerance indicates the need to reconsider indication
and limitations of phlebotomy.
Phlebotomy as a prophylactic measure of risk reduction should result in
mild iron-decient erythropoiesis and hematocrit control. Pharmacologic
cytoreduction is necessary for high risk patients older than 60 years or
with previous thromboembolic complications.
Disclosure Statement:
Regine Wunschel-Nürnberg;Novartis Inc.; Nürnberg; Deutschland
- Beschäigungsverhältnis als Mitarbeiterin bei Novartis
Andreas Hochhaus-Jena;Klinik für Hämatologie und Onkologie; Universitätsk-
linikum Jena; Jena; Deutschland
- Kongresspräsident
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2018
486
Prevalence and Dynamics of BCR-ABL Independent Gene
Mutations in Chronic Phase CML Patients
Lioba Ruppert 1; Jenny Rinke 1; Anja Waldau 1; Markus Prrmann 2;
Andreas Hochhaus 1; Thomas Ernst 1
1Klinik für Innere Medizin II, Onkologisches Forschungslabor,
Universitätsklinikum Jena, Jena, Deutschland
2Institut für medizinische Informationsverarbeitung, Biometrie und
Epidemiologie, Ludwig-Maximilians-Universität München, München,
Deutschland
Purpose: Living without treatment has become a realistic aim for patients
with chronic myeloid leukemia (CML) who achieved durable deep mo-
lecular remission under treatment with tyrosine kinase inhibitors (TKI).
Recently, we have identied novel BCR-ABL independent gene mutations
in newly diagnosed CML patients whereby mutations in epigenetic mod-
ier genes were most common. e prevalence, kinetics and prognostic
signicance of such mutations need to be investigated in a well-charac-
terized patient cohort.
Methods: 100 chronic phase CML patients from the German CML-V (TI-
GER) trial were investigated by targeted deep next-generation sequencing
covering 54 genes frequently mutated in myeloid malignancies. Paired
samples at diagnosis, 12 months, 24 months and 36 months of therapy
were investigated.
Results: Forty-six dierent mutations were detected in 39/100 patients
aecting the genes ASXL1, BCOR, CALR, CUX1, DNMT3A, FBXW7,
IKZF1, JAK2, KDM6A, NOTCH1, RUNX1, STAG2, TET2, TP53, U2AF1
and WT1. ASXL1 (n=13) and DNMT3A (n=9) were most commonly
aected. Nine patients carried more than one mutation. For 26/100 pa-
tients at least one mutation was present at diagnosis. Follow-up samples
revealed that in 22 patients mutations disappeared during TKI treatment.
In 3 patients the mutation persisted indicating that the mutation preced-
ed the BCR-ABL translocation. In 2/97 patients the initial mutation re-
emerged at month 24 aer disappearance at month 12. In 6/100 patients
a new mutation occurred at month 12; 4 of which persisted in further
follow-up samples. Seven mutations were initially detected at month 24
with 2 persisting, and ve mutations at month 36.
Conclusions: BCR-ABL independent gene mutations were frequently
identied in chronic phase CML patients at diagnosis. In a minority of
patients such mutations seem to precede the BCR-ABL translocation in-
dicating a multistep pathogenesis of CML. BCR-ABL independent gene
mutations were found to vary in their dynamics during TKI treatment
and may function as important cofactors in the evolution and persistence
of the disease.
529
Outcome of Refractory and Relapsed Patients with Acute
Myeloid Leukemia
Dietger Niederwieser 1, 1; Rainer Krahl 1; Christoph Kahl 2; Sebastian Scholl 3;
Hans-Heinrich Wolf 4; Michael Cross 1, 5; Ute Hegenbart 6; Norma Peter 7;
Christian Niederwieser 8; Axel Florschütz 9; Kolja F. B. Reifenrath 10;
Niklas Zojer 11; Christian Junghanß 12; Herbert Sayer 13; Volker Schmidt 13;
Georg Maschmeyer 14; Andreas Hochhaus 3; Thomas Fischer 15;
Haifa Kathrin Al-Ali 16; Thomas Heinicke 15
1Universität Leipzig, Leipzig, Deutschland
2Klinikum Magdeburg, Magdeburg, Deutschland
3University Hospital, Jena, Deutschland
4Norbert Kochstr., Nordhausen, Deutschland
5Medical Clinic and Policlinic I, Hematology and Cellular Therapy, Leipzig,
Deutschland
6Universitätsklinikum Heidelberg, Heidelberg, Deutschland
7Department of Internal Medicine, Carl Thieme Klinikum Cottbus, Cottbus,
Deutschland
8Universitätsklinikum , Hamburg Eppendorf, Hamburg, Deutschland
9Klinikum Dessau, Dessau, Deutschland
10Klinikum Oberlausitzer Bergland GmbH, Zittau, Deutschland
11Wien, Österreich
12Klinik für Innere Medizin, Rostock, Deutschland
13Helios Klinikum, Erfurt, Deutschland
14Klinikum Ernst von Bergmann, Potsdam, Deutschland
15Uniklinikum Magdeburg, Magdeburg, Deutschland
16Uniklinikum Halle, Halle, Deutschland
Purpose: Outcome of patients (pts) with refractory Aml or following re-
lapse is usually reported as refractory/relapsed and considered dismal.
Methods: A total of 1621 pts from the OSHO AML 2002 ≤60 y (n=740)
and AML 2004 >60 y (n=881) with newly diagnosed AML (except APL)
eligible for chemotherapy were analyzed. Pts with partial remission (PR)
or non-response (NR) to two induction cycles were considered refractory.
Pts achieving CR and relapsing thereaer were considered relapses and
treated with MitoFlag or Flag-Ida.
Results: A total of 238 (14.7%) pts were refractory (PR 60.1%, NR 39.9%).
OS of refractory pts was 11.4 (7.9-16.6)% @5y, and dependent upon PR
[13.1 (8.1-21.1) % @10y] and NR [5.2 (2.1-12.6)% @5y; p=0.0003]. In-
tensive chemotherapy ± HSCT and hypomethylating agents (HMA)
were able to induce CR in 24.8%. CR pts had an OS of 42.7 (31.4-58.2)
% @5y. Risk factors for OS in refractory pts were age and type of therapy
(p<0.0001). Younger patients with FLT3 mut had a trend for inferior OS
(p=0.1). Almost all long term survivors were treated with HSCT.
Of the 1144 CR/CRi pts, 582 relapsed 1-121 months (mts) aer CR. Age,
cytogenetic risk, type of AML, interval CR to relapse and HSCT were the
dominant factors for relapse. A total of 198 pts received palliative treat-
ment. CR2 was achieved aer intensive chemotherapy ± HSCT, ± DLI
and HMA in 227 pts (39.0%). OS of relapsed pts was 13.8 (11.1 – 17.3) %
@5y. Pts with CR2 had a LFS of 24.9 (19.5-31.7) % @5y and was highest
in patients when intensive chemotherapy followed by HSCT was involved.
Conclusions: Outcome of pts with refractory and relapsed AML is consis-
tent >10% @5y. Age, proportion of palliative treatment and in younger pts
FLT3 mut was recognized as a determinant for OS. However, refractory
and relapsed pts have dierent outcomes and results depend upon PR, NR
and CR. Increase of CR rate in younger but especially in elderly pts with
second generation TKI, reduction of TRM using FLT3-inhibitor mono-
therapy and the option to treat pts ineligible to chemotherapy promise
better outcome.
Disclosure Statement: Cellectis and Daichii
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554
Unfavorable Prognosis of Patients with Acute Myeloid
Leukemia and Central Nervous System Involvement
Sebastian Birndt; Maximilian Fleischmann; Tobias Rachow;
Inken Hilgendorf; Sebastian Scholl; Andreas Hochhaus; Ulf Schnetzke
Universitätsklinikum Jena, Klinik für Innere Medizin II, Jena, Deutschland
Purpose: Central nervous system (CNS) involvement in acute myeloid
leukemia (AML) is rare and associated with a poor outcome. Systematic
data is scarce and cerebrospinal uid puncture (CFP) is not recommended
in current guidelines at any time point of the disease. However, distinct
signs and symptoms should raise awareness of CNS involvement in AML
patients (pts).
Methods: In this retrospective single center analysis, we analyzed 18 AML
pts identied by screening our in-house database using the keywords
meningeosis” and “AML” diagnosed between 2006 and 2019. All pts re-
ceived CFP and blasts were detected in all samples by microscopy and/or
ow cytometry. Further characterization was performed by clinical, mo-
lecular and pathological parameters.
Results: 18 pts (6 female/ 12 male) with a median age of 55 years at diag-
nosis (range, 27-77) were identied. Clinical symptoms were headache,
lack of vigilance, nausea or distinct neurological symptoms like cranial
or peripheral nerve palsies. Besides meningeal involvement, 5 pts (28 %)
also had solid CNS manifestations. 6 pts (33 %) presented with CNS in-
volvement at initial diagnosis, 12 (66 %) at relapse. 9 pts (50 %) under-
went allogeneic stem cell transplantation (SCT), 6 (33 %) had meningeal
relapse aer allogeneic SCT and 3 pts (17%) showed CNS involvement
before allogeneic SCT. Only 2 pts (11 %) are still alive, both of them had
CNS involvement before allogeneic SCT. Median survival aer diagnosis
of CNS involvement was 205 days (range, 2-3475). 16 of 18 pts (88 %)
received intrathecal chemotherapy; in individual cases radiation was ap-
plied. e majority of pts were categorized into adverse and intermediate
risk group according to current ELN guidelines (7 (38%) and 9 pts (50%),
respectively).
Conclusions: ere is an unmet need for a more vigorous screening for
risk factors of CNS involvement in AML pts due to its poor prognosis.
Several risk factors have been identied that might be associated with the
occurrence of CNS involvement in AML pts. Intensied treatment strate-
gies might be benecial to improve outcome in this patient cohort.
702
Novel Circulating Tumor Dna (CTDNA) Based Ddpcr Drop-
OFF Assays for Improved Minimal Residual Disease (MRD)
Monitoring in Acute Myeloid Leukemia (AML)
Christian Rausch 1; Frank Ziemann 1; Stephanie Schneider 1, 2;
Marion Subklewe 1; Karsten Spiekermann 1; Maja Rothenberg Thurley 1;
Klaus Metzeler 1
1Medizinische Klinik und Poliklinik III, Klinikum der Universität München,
Laboratory for Leukemia Diagnostics, Munich, Deutschland
2University Hospital, LMU Munich, Institute of Human Genetics, Munich,
Deutschland
Purpose: MRD assessment is important for early relapse detection in
AML. MRD monitoring by bone marrow (BM) aspiration is more sen-
sitive than analyses of peripheral blood (pB), yet it is invasive. Moreover,
both fail to detect extramedullary disease (EMD). Analyses of ctDNA may
address these limitations.
Methods: Plasma samples were collected in Streck tubes. CtDNA
was isolated using the QIAampCNA Kit and quantied by Agilent
2100 Bioanalyzer High Sensitivity DNA Kit. Mutations in IDH2 and
NPM1 were detected using custom drop-o ddPCR assays (BioRad
QX200). Mutations in IDH1 and DNMT3A were detected using
commercially available ddPCR assays (Biorad). All assays achieved
<0.1% sensitivity. All patients provided written informed consent.
Results: We regularly monitored ctDNA, bulk pB cell and BM gDNA in
13 patients with previously untreated AML during induction therapy with
the following mutations: NPM1 (Type A, n=7; Type V, N=1), DNMT3A
(R882H, n=4), IDH1 (R132H, n=1) and IDH2 (R140Q, n=2; R172K, n=2).
Variant Allele Frequencies (VAF) of BM- and ctDNA-samples correlated
closely. Sensitivity of ctDNA samples was similar to ddPCR analyses of
BM gDNA, and superior to pB cell gDNA. Mutations were detectable in
ctDNA beyond pB blast clearance, and in one case a mutation present
in EMD but not in BM was detected in ctDNA, indicating that ctDNA
noninvasively captures relevant disease compartments. Absolute
ctDNA levels correlated closely to known causes of cell turnover such
as infections or BM regeneration. However, in cases in which both
mutation VAF and absolute ctDNA levels rose, AML progressed.
Conclusions: We are currently investigating the prognostic value of
response kinetics during treatment. Patient recruitment is ongoing, and
updated data will be presented. ddPCR-based ctDNA analysis allows
minimally invasive AML monitoring. ctDNA analyses may be more
sensitive than pB-cell gDNA and may capture EMD.
Disclosure Statement: e authors have no conicts of interest to disclose.
742
MARS: Mutation-Adjusted Risk Score for Advanced Systemic
Mastocytosis
Mohamad Jawhar 1; Juliana Schwaab 1; Iván Álvarez-Twose 2;
Khalid Shoumariyeh 3; Nicole Naumann 1; Johannes Lübke 1;
Cecelia Perkins 4; Javier I Muñoz-González 2; Manja Meggendorfer 5;
Vanessa Kennedy 6; Georgia Metzgeroth 1; Alice Fabarius 1;
Dietmar Pfeifer 3; Karl Sotlar 7; Hans-Peter Horny 8; Nikolas von Bubno 3;
Torsten Haferlach 5; Nicholas C.P. Cross 9; Wolf-Karsten Hofmann 1;
Wolfgang R. Sperr 10; Andrés C García-Montero 2; Peter Valent 10;
Jason Gotlib 6; Alberto Orfao 2; Andreas Reiter 1
1Hematology and Oncology, University Hospital Mannheim, Heidelberg
University, Mannheim, Germany
2Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain
3Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty
of Medicine, University of Freiburg, Freiburg, Germany
4^Division of Hematology, Department of Medicine, Stanford University School
of Medicine/Stanford Cancer Institute, Stanford, United States
5Munich Leukemia Lab (MLL), Munich, Germany
6Division of Hematology, Department of Medicine, Stanford University School
of Medicine/Stanford Cancer Institute, Stanford, United States
7Institute of Pathology, Medical University of Salzburg, Salzburg, Austria
8Institute of Pathology, Ludwig-Maximilians-Universit, Munich, Germany
9Wessex Regional Genetics Laboratory, Salisbury, United Kingdom
10Internal Medicine I, Division of Hematology and Hemostaseology, Ludwig
Boltzmann Institute for Hematology and Oncology, Medical University of
Vienna, Vienna, Austria
Purpose: With the aim to establish a prognostic score for advanced sys-
temic mastocytosis (AdvSM), we evaluated a large cohort of clinically and
genetically well characterized patients who were enrolled within the ‘Ger-
man Registry on Disoders of Eosinophils and Mast Cells. e proposed
mutation-adjusted risk score (MARS) was subsequently validated in an
independent cohort of AdvSM patients derived from several centers with-
in the European Competence Network on Mastocytosis (ECNM).
Methods: A total of 383 AdvSM patients were included. e diagnosis
of AdvSM was established according to the WHO classication. Molec-
ular analyses were performed at diagnosis. Targeted Next-Generation Se-
quencing (NGS) was performed to investigate mutation status of KIT and
32 myeloid genes.
Results: In multivariable analysis, the following risk factors were iden-
tied as being associated with overall survival (OS): age greater than 60
years, anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelets < 100
< 109/L), presence of one high molecular risk gene mutation (ie, in SRSF2,
ASXL1, and/or RUNX1), and presence of two or more high molecular risk
gene mutations. By assigning hazard ratio–weighted points to these vari-
ables, the following three risk categories were dened: low risk (median
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OS, not reached), intermediate risk (median OS, 3.9 years; 95% CI, 2.1 to
5.7 years), and high risk (median OS, 1.9 years; 95% CI, 1.3 to 2.6 years;
P < .001). e MARS was independent of the WHO classication and
was conrmed in the independent validation set. During a median fol-
low-up time of 2.2 years (range, 0 to 23 years), 63 (16%) of 383 patients
experienced a leukemic transformation to secondary mast cell leukemia
(32%) or secondary acute myeloid leukemia (68%). e MARS was also
predictive for leukemia-free survival (P < .001).
Conclusions: e MARS is a validated, ve-parameter, WHO-indepen-
dent prognostic score that denes three risk groups among patients with
AdvSM and may improve up-front treatment stratication for these rare
hematologic neoplasms.
Disclosure Statement: nothing to disclose
744
Accurate and Reproducible Measurement of BCR-ABL1 (IS)
Using Digital PCR: Results from a EUTOS Ring Trial
Georg-Nikolaus Franke 1; Niels Pallisgaard 2; Jacqueline Maier 1;
Kathrin Wildenberger 1; Katerina Machova Polakova 3; Matthew Salmon 4;
Nicholas C. P. Cross 4; Helen E. White 4; Guiseppe Saglio 5; Enrico Gottardi 5;
Simona Soverini 6; Andreas Hochhaus 7; Dietger Niederwieser 8;
Thoralf Lange 8, 9; Thomas Ernst 7
1Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I, Leipzig,
Deutschland
2Zealand University Hospital, Roskilde, Dänemark
3Institute of Hematology and Blood Transfusion, Department of Molecular
Genetics, Prague, Tschechien
4Wessex Regional Genetics Laboratory, Salisbury, United Kingdom
5University of Turin, Department of Clinical and Biological Sciences, Medicine
and Molecular Oncology Laboratories, Turin, Italien
6Bologna University, Department of Experimental, Diagnostic and Specialty
Medicine, Bologna, Italien
7Universitätsklinikum Jena, Klinik für Innere Medizin II, Jena, Deutschland
8Universität Leipzig, Medizinische Fakultät, Leipzig, Deutschland
9Asklepios Klinikum Weißenfels, Klinik für Hämatologie, internistische Onkologie
und Gastroenterologie, Weißenfels, Deutschland
Purpose: BCR-ABL1 positive chronic myeloid leukemia is monitored by
quantitative PCR (RTqPCR). To compare results between dierent labora-
tories alignment to the International Scale (IS) using a conversion factor
(CF) is required, involving a cumbersome process of sample exchange or
lyophilized cell reference material (the LYO-panel)1. We evaluated digital
PCR (dPCR) for monitoring BCR-ABL with regards to interlaboratory
variation, ability to detect deep molecular responses and the CF within the
European Treatment and Outcome Study for CML (EUTOS) consortium.
Methods: Assays for BCR-ABL1 and the reference genes (RG) ABL1 (pro-
vided by Bio-Rad) and BCR (provided by NP) were shipped to 7 laborato-
ries together with the LYO Panel. Samples were prepared and measured in
quadruplicate on two days using local RNA extraction and reverse tran-
scription and the provided assays. Valid results were returned from 6 labs
for central analysis.
Results: Mean %BCR-ABL1/ABL1 for MR1 to MR4.5. was 14.99% (range,
12.23 – 16.95%), 1.36% (0.97 – 1.68%), 0.109% (0.080 – 0.139%), 0.0128%
(0.0105 – 0.0143%) and 0.0081% (0.0022 – 0.0182%), respectively, and
17.11% (14.09 – 23.46%), 1.25% (1.08 – 1.42%), 0.111% (0.090 – 0.135%),
0.0095% (0.0080 – 0.0120%) and 0.0064% (0.0032 – 0.0089%) for BCR-
ABL1/BCR, respectively. %CV for ABL1 and BCR as RG, ranged from
11.3 for MR1 (%BCR-ABL/RG< 10%) to 78.9 for MR4.5 samples. CF to
IS could be calculated for 4/6 labs for BCR and was 0.954 (mean, range
0.868 – 1.097), compared to only 2/6 labs for ABL1 with a mean CF of
1.023 (range 0.851-1.204). e main reason for not being able to calculate
a CF was non-linearity at MR4.5.
Conclusion: Digital PCR reliably detects deep molecular responses. Inter-
laboratory variation was low and the calculated CFs for individual labs lay
within a very narrow band, suggesting that digital PCR might overcome
the need for a lab specic CF. is needs to be tested in a larger trial using
optimized PCR settings for both assays.
Reference:
1. Cross NCP et al. Leukemia 2016
Disclosure Statement: e authors have nothing to disclose.
747
Prognostic Signicance of BAALC and MN1 Expression Levels
During Disease Course in Acute Myeloid Leukemia (AML)
Patients Receiving Allogeneic Stem Cell Transplantation
(HSCT)
Madlen Jentzsch; Marius Bill; Juliane Grimm; Julia Schulz;
Karoline Goldmann; Dominic Brauer; Dietger Niederwieser;
Uwe Platzbecker; Sebastian Schwind
Hämatologie, Zelltherapie, Internistische Onkologie und Hämostaseologie,
Universitätsklinikum Leipzig, Leipzig, Deutschland
Purpose: High pre-treatment expression of the AML-associated genes
BAALC (brain and acute leukemia, cytoplasmic) & MN1 (meningioma-1)
links to adverse outcomes in patients (pts) receiving chemotherapy. e
prognostic signicance in pts receiving allogeneic HSCT for consolida-
tion remains to be elucidated.
Methods: We analyzed 138 AML pts receiving non-myeloablative (3x30
mg/m2 Fludarabine & 2 Gy total body irradiation) allogeneic HSCT (me-
dian age 64, range 32-76 years [y]) in complete remission (CR) or CR with
incomplete recovery (CRi). Digital droplet PCR was applied to quantify
absolute pre-treatment bone marrow BAALC & MN1 copy numbers. For
66 pts, pre-HSCT peripheral blood BAALC & MN1 copy numbers were
assessed in CR/CRi. Rs OptimalCutpoint package dened high & low ex-
pressers, pre-treatment & pre-HSCT respectively. At diagnosis recurrent
mutations by next generation sequencing & ow cytometry patterns were
analyzed. Median follow up was 6.3y.
Results: High pre-treatment BAALC & MN1 copy numbers associated
with a higher CD34 (P<.001 & P<.001, respectively) & CD34+/CD38-
surface antigen expression on mononuclear cells at diagnosis (P<.001 &
P<.001), lower incidence of normal karyotype (P=.008 & P=.04), worse
ELN risk (P=.02 & P=.05), NPM1 wild type (P<.001 & P<.001) & RUNX1
mutations (P=.03 & P=.01). ere was no correlation between pre-treat-
ment & pre-HSCT BAALC (r=.14) or MN1 copy numbers (r=-.06). High
pre-treatment BAALC & MN1 copy numbers associated with higher cu-
mulative incidence of relapse (CIR, P=.05 & P=.05) while overall surviv-
al (OS) was not signicantly dierent (P=.61 & P=.41). In contrast, we
observed a signicantly higher CIR for pts with high pre-HSCT BAALC
(P=.05) or MN1 copy numbers (P=.01) which also translated into shorter
OS (P=.003 & P=.004).
Conclusions: While the adverse prognostic eects of high BAALC & MN1
expression at AML diagnosis might be mitigated aer allogeneic HSCT,
high BAALC or MN1 expression in CR/CRi prior to allogeneic HSCT may
detect residual disease & identify patients at high risk of relapse & shorter
survival.
754
TET2 Mutation Associated Clonal Hematopoiesis is Linked to a
TET2 Polymorphism in Acute Myeloid Leukemia Patients
Dominic Brauer; Juliane Grimm; Madlen Jentzsch; Marius Bill;
Karoline Goldmann; Julia Schulz; Dietger Niederwieser;
Uwe Platzbecker; Sebastian Schwind
University Hospital Leipzig, Medical Clinic and Policlinic 1, Hematology and
Cellular Therapy, Leipzig, Deutschland
Purpose: TET2 mutations (mut) can be detected in complete remission
(CR), as persistent clonal hematopoiesis (CH), in about 16% of acute my-
eloid leukemia (AML) patients (pts). Several TET2 single nucleotide poly-
morphisms (SNPs) represent missense variants and are linked to altered
gene expression. We analyzed the TET2 coding region for CH associated
SNPs in AML.
Methods: Using a next-generation targeted amplicon sequencing (TAS)
approach we analyzed TET2 exons 3–11 in bone marrow samples at
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diagnosis (dx) in 111 AML pts (median age 64, range 33-75 years) on
the MiSeq platform (Illumina). In a subset of 75 pts in CR or CR with
incomplete recovery (CRi) peripheral blood was tested for CH associat-
ed mut (i.e. in ASXL1, DNMT3A, IDH1, IDH2, IKZF1, JAK2, PPM1D,
SF3B1, SRSF2 & TET2) applying TAS. Mut with variant allele frequency
(VAF) <3% were excluded from further analyses. Outcome analyses were
performed in 102 of these pts; receiving allogeneic hematopoietic stem
cell transplantation (HSCT) in CR/CRi. Median follow up was 6.0 years.
Results: In TET2 SNP rs34402524 (c.5162T>G; p.Leu1721Trp) minor al-
lele (G) presence vs absence associated with TET2 CH mut (26% vs 5%,
P=.02), but not with the presence of CH mut in one of the other analyzed
genes, e.g. in DNMT3A. TET2 SNP rs34402524 allele distribution was
86% T & 14% G. e minor allele SNP frequency in AML was comparable
to healthy caucasians (12% GnomAD; P=.18). e incidence of TET2 mut
at dx did not dier between pts with minor allele (G) presence vs absence
(18% vs 26%, P=.41). e mean VAF of TET2 CH mut did not vary for
pts with minor allele (G) presence vs absence (21% vs 32%, P=.49). Pts
with minor allele (G) undergoing HSCT were by trend less likely to suer
relapse (32% vs 53%, P=.08), but had no dierent overall survival (P=.70).
Conclusions: We found the minor allele (G) in TET2 SNP rs34402524 to
be linked to TET2 mut associated CH in AML pts, but not to the presence
of TET2 mut at dx. Further analyses of a larger set of pts and function-
al studies will improve our understanding of TET2 mut associated CH
in AML.
755
Comparison of Four Dierent Humanized Hematopoietic
Niche Xenotransplantation Models to Engraft Myelodysplastic
Syndromes (MDS)
Eva Altrock 1; Carla Sens-Albert 1; Johann-Christoph Jann 1;
Johanna Flach 1; Vladimir Ryabov 1; Nanni Schmitt 1; Alexander Streuer 1;
Qingyu Xu 1; Verena Nowak 1; Justine Danner 1; Julia Obländer 1; Nina
Draeger 1; Iris Palme 1; Ahmed Jawhar 2; Cleo-Aron Weis 3; Vanessa Weyer 4;
Florian Nolte 1; Georgia Metzgeroth 1; Alexander Marx 3;
Christoph Groden 4; Wolf-Karsten Hofmann 1; Daniel Nowak 1
1Department of Hematology and Oncology, Medical Faculty Mannheim,
Heidelberg University, Mannheim, Deutschland
2Department of Orthopedics and Traumatology, Medical Faculty Mannheim,
Heidelberg University, Mannheim, Deutschland
3Institute of Pathology, Medical Faculty Mannheim, Heidelberg University,
Mannheim, Deutschland
4Department of Neuroradiology, Medical Faculty Mannheim, Heidelberg
University, Mannheim, Deutschland
Purpose: Xenogra models in NSG mice have emerged as versatile
preclinical platforms for investigation of functional pathomechanisms
in MDS ([1] Medyouf et al., 2014, [2] Rouault-Pierre et al., 2017). e
limiting factor of these models is the low engrament of patient-derived
CD34+ hematopoietic stem cells (HSCs). Ecient humanized 3D scaf-
folds in NSG mouse models have been established, enabling to increase
engrament rates of normal and malignant hematopoiesis ([3] Reinisch et
al., 2016current models do not fully mimic the components of the human
bone marrow (BM, [4] Abarrategi et al., 2017). erefore, we evaluated
engrament ability of IPSS low-risk, int-1 and high-risk-patient samples,
in four dierent 3D scaolds.
Methods: We transplanted samples from 10 MDS patients in parallel into
NSG mice testing the following conditions: A) Intrafemoral co-injection
of CD34+ HSCs and MSCs according to [1]. Subcutaneous implantation
of 3D scaolds. Gelfoam (B) and Bio-OSS (C) [4], Matrigel ossicles (D)
[3] and primary human bone isolated aer hip replacement, inserted with
Gelfoam, preseeded in vitro with MSCs and mononuclear cells (MNCs)
and injected in vivo with CD34+ HSCs 8 weeks aer implantation (hu-
man bone ossicles = HBO) (E).
Results: Gelfoam and HBO showed signicantly higher hCD45+cell
numbers compared to intrafemoral injection analyzed by ow cytome-
try. We found systemic engrament of hCD45+cells outside the injected
bone fragment in the BM and spleen solely in mice, which received HBO.
is could possibly be explained due to transplantation of MNCs in this
condition. at was supported by another set of experiments using HBO
(n=10), which showed that colonization of the scaold was similar when
transplanting either CD34+ cells + MSCs, MNCs + MSCs or MNCs only
but systemic engrament could only be seen in MNC transplanted mice.
Conclusions: Our data show that hCD45+cells and MSCs from MDS BM
were able to colonize humanized ossicle scaolds. Gelfoam and HBO were
the most promising novel methods to improve MDS xenogra models.
For systemic engrament, application of MNCs seems to be necessary.
Disclosure Statement: nothing to disclose
781
Treatment with Romiplostim in Patients with Lower-Risk
Myelodysplastic Syndrome (MDS) and Thrombocytopenia -
Results of the Europe Trial By the Emsco Network
Anne Sophie Kubasch 1; Aristoteles Giagounidis 2; Georgia Metzgeroth 3;
Anna Jonasova 4; Regina Herbst 5; José Miguel Torregrosa Diaz 6;
Benoit De Renzis 7; Katharina Götze 8; Marie-Luise Hütter-Krönke 9;
Marie-Pierre Gourin 10; Sophie Dimicoli-Salazar 11;
Pascale Cony-Makhoul 12; Sophie Park 13; Katja Jersemann 14;
Oliver Tiebel 15; Katja Sockel 16; Silke Gloaguen 17; Anna Mies 16;
Fatiha Chermat 18; Christian Thiede 16; Rosa Sapena 18; Richard F Schlenk 19;
Pierre Fenaux 20; Lionel Ades 20; Uwe Platzbecker 1
1Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig
University Hospital, Leipzig, Deutschland
2Department of Oncology, Hematology and Palliative Care, Marien Hospital
Düsseldorf, Düsseldorf, Deutschland
3Department of Hematology and Oncology, University Medical Centre
Mannheim, Mannheim, Deutschland
4Department of Hematology, First Faculty of Medicine, Charles University and
General University Hospital, Prague, Tschechien
5Internal Medicine III, Department of Hematology, Oncology, Stem Cell
Transplantation, Klinikum Chemnitz gGmbH, Chemnitz, Deutschland
6Department of Hematology and Oncology, CHU de Poitiers, Poitiers, Frankreich
7Service d’Hématologie, CHU Clermont‐Ferrand, Clermont‐Ferrand, Frankreich
8Medical Department III for Hematology and Oncology, Klinikum rechts der Isar,
Technische Universität München, München, Deutschland
9Department of Internal Medicine III, University of Ulm, Ulm, Deutschland
10CHRU de Limoges, Limoges, Frankreich
11Department of Hematology, Hôpital Haut Lévèque, University Hospital
Bordeaux, Pessac, Frankreich
12Centre Hospitalier Annecy Genevois, Épagny-Metz-Tessy, Frankreich
13Department of Hematology, CHU Grenoble-Alpes, Grenoble, Frankreich
14GWT-TUD GmbH, Dresden, Deutschland
15Institute of Clinical Chemistry and Laboratory Medicine, University Hospital
Dresden, Technical University of Dresden, Dresden, Deutschland
16Medical Clinic and Policlinic 1, University Hospital Dresden, Dresden,
Deutschland
17The European MDS studies cooperative group (EMSCO), www.emsco.eu
18Groupe Francophone des Myélodysplasies (GFM), Paris, Frankreich
19Department of Internal Medicine V, Heidelberg University Hospital,
Heidelberg, Deutschland
20Hématologie clinique, Hôpital Saint-Louis, Paris, Frankreich
Purpose: e thrombopoietin receptor agonist (TPO-RA) romiplostim
has shown safety and ecacy in a poorly-dened subset of lower-risk (LR)
myelodysplastic syndrome (MDS) patients with thrombocytopenia.
Methods: e EUROPE multicenter phase 2 trial investigated the im-
pact of endogenous thrombopoietin (TPO) level and platelet transfusion
events (PTE) on the ecacy of romiplostim treatment in patients with LR-
MDS (IPSS low/int-1). Patients were eligible if baseline bone marrow blast
count was <5% and platelet counts were ≤30 G/L or ≤50 G/L in case of
bleeding history. Patients were assigned into 3 dierent cohorts at the time
of screening based on their previous PTE and TPO serum levels (cohort
A TPO<500 ng/l, PTE<6U/past year; cohort B: TPO<500 ng/l, PTE≥6U
or TPO≥500 ng/l, PTE<6U, cohort C: TPO≥ 500 ng/l, PTE≥6U). Primary
endpoint of the study was the rate of hematologic improvement of plate-
lets (HI-P) according to IWG 2006 criteria aer 16 weeks of romiplostim
treatment.
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Results: A total of 68 patients with a median platelet count of 25 G/L
(range 1-50 G/L) were included and stratied into cohort A (n=47), B
(n=17) or C (n=4), respectively. Two patients had transient increases in
peripheral blasts to >10% and 1 patient progressed to AML aer 1 month
of treatment. HI-P was observed in 26 of 68 (38%) patients, while re-
sponse was ongoing in 24 of them beyond week 16. Rate of HI-P lasting
for at least 8 weeks was higher in cohort A (45%) compared to patients in
cohort B and C (24%) (p=0.11). Explorative analysis showed a correlation
between pretreatment PTE and endogenous TPO-levels (p=0.034). Eval-
uation of the mutational prole in a subgroup of 49 patients demonstrat-
ed that 67% of responders exhibited spliceosome mutations compared to
35% in non-responders (p=0.06).
Conclusions: e EUROPE study conrms that romiplostim treatment
is eective in a subgroup of LR-MDS patients, neither baseline PTE nor
baseline TPO levels were signicantly associated with response. Further
translational studies are ongoing to elucidate biomarkers of response.
Disclosures: Study funding from Amgen
Lung Cancer
Poster
181
Treatment Patterns of EGFR MT+ NSCLC IV PTS: Real World
Data of the Nowel Network
Julia Roeper 1, 2; Markus Falk 2, 3; Katrin Wedeken 4; Ursula Stropiep 4;
Markus Tiemann 2, 3; Lukas C. Heukamp 2, 3; Claas Wesseler 5;
Sandra Sackmann 6; Frank Griesinger 1, 2
1Universitätsklinik Innere Medizin-Onkologie Carl v. Ossietzky Universität
Oldenburg, Pius Hospital Oldenburg, Oldenburg, Deutschland
2Lung Cancer Network NOWEL.org Oldenburg, Oldenburg, Deutschland
3Institut für Hämatopathologie Hamburg, Hamburg, Deutschland
4Pius Hospital Oldenburg, Oldenburg, Deutschland
5Asklepios Klinikum Harburg, Hamburg, Deutschland
6Klinikum Bremen-Ost, Bremen, Deutschland
Purpose: e percentage of pts switching from 1st gen TKI in 1st line to 3rd
gen TKI in 2nd line seems to be low with 30% and it is questionable wheth-
er these data represent real world treatments1. erefore, we investigated
the treatment pattern and especially the attrition rate between 1st and 2nd
line therapy in EGFR mt+ pts.
Methods: 965/1536 (63%) pts with non-squamous NSCLC IV were test-
ed for EGFR mt+. 148/965 (15%) pts with an EGFR mt+ were identied.
To calculate PFS and OS we used Kaplan Meier and the log rang test for
p-values.
Results: 144/148 pts were treated with TKI on 1st or 2nd line (aer chemo-
therapy). 14/144 pts are still on 1st line, 9 pts were lost to follow-up and
3 pts died while on 1st line. We identied 118/144 candidates for 2nd line
therapy (because of progression on 1st line TKI) and only 84/118 (70%)
pts received a 2nd line therapy. 30% (36/118) of pts did not receive a 2nd
line therapy because of bad PS (n=26), pts refusal (n=2), fast progression
(n=6) and death (n=2). Aer accessibility of 3rd gen TKI 72 pts were candi-
dates for 2nd line treatment and 51/71 pts (71%) received a 2nd line therapy.
mOS of pts receiving 2nd line therapy aer access to 3rd gen TKI was 35 mo
for pts with 2nd line therapy vs. 10 mo without 2nd line (p<0.000). 32/51
pts (63%) were tested for T790M and 20/32 (62%) were T790M+. Highest
T790M test rate in one center was 22/28 (79%). 16/20 (80%) T790M+ pts
received 3rd gen TKI for 2nd line therapy. mOS of pts receiving 3rd gen TKI
(n=31) was 51 mo vs. 25 mo for pts without 3rd gen TKI (p<0.002).
Conclusions: A signicant number of pts treated with 1st or 2nd gen TKI
do not reach 2nd line therapy even with broad accessibility of 3rd gen TKI.
Reasons for not receiving 2nd line therapy are in most cases deterioration
of PS, death and no testing for T790M in a minority of cases. ese data
are important for the interpretation of the OS data of the FLAURA study1
as they reect real world treatment algorithms in dedicated German lung
cancer centers.
Reference:
1. Soria J-CH et al. Osimertinib in Untreated EGFR-Mutated Advanced Non–
Small-Cell Lung Cancer. N Engl J Med 2018; 378:113-125
Conicts of Interest:
Julia Roeper: Honorarium: Roche, Boehringer Ingelheim
Markus Falk: e authors declare no potential conict of interest.
Ursula Stropiep: e authors declare no potential conict of interest.
Markus Tiemann: Honorarium: Astra Zeneca, Boehringer Ingelheim, Novartis,
Roche, Pzer, Takeda, BMS, MSD
Travel costs: Boehringer Ingelheim, Roche, Takeda, BMS, MSD
Lukas C. Heukamp: Honararium: NEO New Oncology, BMS, Bayer, Roche, Pzer
Advisory board: NEO New Oncology, BMS, Bayer, Roche, Pzer
Class Wessler: e authors declare no potential conict of interest.
Sandra Sackmann: e authors declare no potential conict of interest.
Frank Griesinger: Honorarium: Astra Zeneca, Boehringer Ingelheim, BMS,
Celgene, Lilly, MSD, Novartis, Pzer, Roche, Takeda, Ariad, Abbvie, Siemens
Advisory board: ASTRA, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pzer,
Roche, Takeda, Ariad, Abbvie, Siemens
Research fund: Astra Zeneca, Boehringer, BMS, Celgene, Lilly, MSD, Novartis,
Pzer, Roche, Takeda, Siemens
190
Sophisticated Epitope Quality-Based Approach Reveals
Patient’s Suitability for Immune Checkpoint Inhibition
Michael Wessolly 1, 2; Susann Stephan-Falkenau 3; Anna Streubel 3;
Robert Werner 3; Sabrina Borchert 1, 2; Sergej Gri 4; Elena Mairinger 1;
Robert Walter 1, 5; Torsten Bauer 4; Wilfried Eberhardt 5, 6;
Torsten Gerriet Blum 4; Kurt Werner Schmid 1; Jens Kollmeier 4;
Thomas Mairinger 3; Fabian Dominik Mairinger 1, 2
1Universitätsklinikum, Institut für Pathologie, Essen, Deutschland
2German Cancer Consortium (DKTK), Partner Site University Hospital Essen,
Essen, Deutschland
3Helios Klinikum Emil von Behring, Fachbereich Gewebsdiagnostik/Pathologie,
Berlin, Deutschland
4Helios Klinikum Emil von Behring, Lungenklinik Heckeshorn, Berlin,
Deutschland
5Ruhrlandklinik, Westdeutsches Lungenzentrum, Essen, Deutschland
6Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen,
Deutschland
Purpose: Immune checkpoint inhibition, especially the blockade of PD-1
and PD-L1, has developed into one of the most prosperous therapeutic
approaches in modern oncology. Despite promising clinical results, re-
sistance acquirement remains a perpetual problem1. One possible escape
mechanism, which mediates therapy failure might be linked altered epi-
tope processing (processing escapes)2. In the present study, we aim to
demonstrate the eects of processing escapes on immunotherapy out-
come in NSCLC-patients.
Methods: e cohort was comprised of primary tumor samples from
48 NSCLC-patients. Everyone received Nivolumab at one point of
their treatment. Mutations were identied by targeted amplicon-
based sequencing including hotspots and whole exomes of 22 genes.
Convolutional neural networks were utilized to examine the eect of
mutations on proteasomal processing. e algorithm was previously
trained on 1260 known MHC-I ligands. Possible inuences on Overall
survival were calculated by Cox-regression.
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Results: In the validation cohort, patients displaying both processing
escapes and high expression rates PD-L1 (n=8/48) showed signicantly
shortened overall survival, independent of mutational load or PD-L1 sta-
tus alone in multivariate analysis.
Conclusions: e concept of altered epitope processing might broaden
our horizon in understanding immune therapy failure. Especially when
combined with PD-L1 status, this method could provide important neg-
ative predictive value, potentially becoming a foundation in the I/O ther-
apy decision process.
References:
1. Wessolly M, Mairinger F. Processing Escapes: A New Perspective on Im-
mune Escape Mechanisms. Canc erapy & Oncol Int J. 2017;5(3):CTOIJ.
MS.ID.555662.
2. Wessolly M, Walter RFH, Vollbrecht C, et al. Processing Escape Mecha-
nisms rough Altered Proteasomal Cleavage of Epitopes Aect Immune
Response in Pulmonary Neuroendocrine Tumors. Technol Cancer Res Treat.
2018;17:1533033818818418.
Disclosure Statement: All authors formally declare that there are no conicts of
interest
201
Long Time Remission in NSCLC Stage iv After Stopping
Immunotherapy Due to Severe Side Eects - a Report
of Two Cases
Helge G. Bischo 1; Christiane Wiedemann 1; Maria Sianidou 2;
Petros Christopoulos 2; Claus Peter Heußel 2; Michael Thomas 2
1Thoraxklinik, Heidelberg, Deutschland
2Thoraxklinik, Radiologie, Heidelberg, Deutschland
Purpose: Immunotherapy is an important element in the treatment of
NSCLC. Side eects of immunotherapy due to autoimmune reactions can
lead to severe problems.
Methods: We report two cases with long time remission aer stop of Im-
munotherapy due to side eects
Results:
Case 1: A 62 y old male was diagnosed with NSCLC; adeno cancer stage
IV in September 2017. No targetable mutations were found, PDL1 was
50%. An Immunotherapy with Pembrolizumab was initiated in October.
CT scan in December 2017 demonstrated PR. Brain metastases were ir-
ridiated in November and December 2017. In December, the patient de-
veloped interstitial pneumonia WHO grade 3 and was treated with high
dose corticosteroids. e immunotherapy was therefore terminated aer
2 cycles in 2017. e patient shows still stable disease without progression
until August 2019.
Case 2: A 61 y old male was diagnosed with NSCLC; adeno cancer stage
IV in January 2017. No targetable mutations were found, PDL1 was 60%.
An immunotherapy with Pembrolizumab was initiated in February 2017.
e CT Scan showed PR aer 4 cycles in May 2017 and SD aer 12 cycles
in November 2017. In November 2017 the patient developed autoimmune
colitis WHO grade 3 and was treated with high dose corticosteroids.
e immunotherapy was therefore terminated aer those 12 cycles. e
patient shows still stable disease without progression until August 2019.
Conclusions:
When immunotherapy has reached a remission and has to be terminated
due to immunologic complications, the complications have to be treated
with immunosuppressive therapy. Aer the remission of the side eects,
the patients might be followed up without systemic therapy under close
clinical observation. In some cases, SD persists. Further tumor-specic
therapy should be only considered, if PD is documented.
238
Delays and Delaying Factors from Symptoms to Diagnosis
in Lung Cancer
Lisa Pisotska 1, 2; Linda Regber 3; Dieter Wuerein 1, 2; Heide Wagner 2;
Joachim Ficker 1, 2; Wolfgang Brückl 1, 2
1Paracelsus Medizinische Privatuniversität Nürnberg, Paracelsus Medical
University, Nürnberg, Deutschland
2Klinikum Nürnberg Nord, Nordklinikum, Department of Respiratory Medicine,
Lung Cancer Center, Nürnberg, Deutschland
3MediStatis.de, Berlin, Deutschland
Purpose: e majority of lung carcinomas are diagnosed and treated in a
late stage. One reason might be long delays between rst symptoms, diag-
nosis and treatment. is study was conducted to identify delays during
the management of patients with lung cancer to assess possible causes for
these delays and to analyze the impact of delays on survival.
Methods: Patients with recently diagnosed lung cancer were prospectively
included. Delays were calculated as: patients delay (rst symptom to rst
general practitioner visit); GP delay (rst GP visit to specialist appoint-
ment); specialists delay (specialist appointment to hospital referral); hos-
pital delay (hospital referral to diagnosis) and treatment delay (diagnosis
to therapy initiation). Delays were analyzed in relation to clinical char-
acteristics and factors for delays were assessed by uni- and multivariate
analyses.
Results: 220 patients were included (60.9% male; median age of 63.5
years; 30.3% SCLC, 77.7% ex-smokers). e median patients delay, GP
delay, specialist’s delay, hospital delay and treatment delay was 5 days
(mean 20.9), 15 days (mean 38.9), 11 days (mean 27.2), 8 days (mean 14.3)
and 15 days (mean 21.4) respectively. Diagnostic intervals were shorter
for patients with SCLC vs NSCLC (median 10.5 vs 16 days, p=0.004) and
for late-stage vs early-stage cancer (median 6 vs 9 days, p=0.025). Patients
<65 years had longer total delay vs those ≥65 years (median 66 vs 49 days,
p=0.035). Patients with dyspnea, cough or hemoptysis had longer patient’s
delay than those without (median 5 vs 3 days, p=0.020), but a shorter
treatment delay (median 14 vs 19 days, p=0.048). No signicant eect on
survival was observed in this cohort.
Conclusions: ere are varieties of causes leading to delays during the
diagnosis of lung cancer. is study provides some insights, which may
help to reduce waiting times by raising awareness of certain demographics
and symptoms and shortening the referral times to improve the overall
outcome for lung cancer patients.
Disclosure Statement: e authors declare that there is no conict of interest.
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242
Relay: a Multinational, Double-Blind, Randomized Phase 3
Study of Erlotinib (ERL) in Combination with Ramucirumab
(RAM) or Placebo (PL) in Previously Untreated Patients with
Epidermal Growth Factor Receptor Mutation-Positive (EGFRM)
Metastatic Non-Small Cell Lung Cancer (NSCLC)
Kazuhiko Nakagawa 2; Edward Garon 3; Takashi Seto 4; Makoto Nishio 5;
Santiago Ponce Aix 6; Chao-Hua Chiu 7; Keunchil Park 8; Silvia Novello 9;
Ernest Nadal 10; Fumio Imamura 11; Kiyotaka Yoh 12; Jin-Yuan Shih 13;
Kwok Hung Au 14; Denis Moro-Sibilot 15; Sotaro Enatsu 16;
Bente Frimodt-Moller 17; Carla Visseren-Grul 18;
Annamaria H. Zimmermann 19; Martin Reck 1
1Großhansdorf, Lungenclinic, Großhansdorf, Deutschland
2Kindai University Hospital, Department of Medical Oncology, Osakasayama,
Japan
3David Geen School of Medicine, University of California, Los Angeles,
United States
4National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
5Department of Thoracic Medical Oncology, , The Cancer Institute Hospital
of Japanese Foundation for Cancer Research, Tokyo, Japan
6Hospital 12 De Octubre, Madrid, Spanien
7Veterans General Hospital, Taiwan
8Samsung Seoul Hospital, Cancer Hospital, Seoul, Südkorea
9Department of Oncology, University of Turin, Orbassano, Italien
10Institut Català d‘Oncologia - L‘Hospitalet de Llobregat, L‘Hospitalet de
Llobregat, Spanien
11Osaka internatioanl cancer center, Osaka, Japan
12National Cancer Center Hospital East, Kashiwa, Japan
13National Taiwan University Hospital, Taipei, Taiwan
14Queen Elizabeth Hospital, Hong kong, Hong Kong
15University Hospital, Grenoble, Frankreich
16Eli Lilly Japan KK, Kobe, Japan
17Eli Lilly Denmark A / S, Herlev, Dänemark
18Lilly Netherlands, Utrecht, Niederlande
19Eli Lilly and Company Corporate Center, Indianapolis, United States
Purpose: RELAY evaluated ecacy and safety of erlotinib (ERL)+ramu-
cirumab (RAM) or placebo (PL) in 1L epidermal growth factor receptor
mutation-positive (EGFRm) metastatic non-small cell lung cancer (NS-
CLC).
Methods: Eligibility: untreated metastatic NSCLC patients (pts) with
Exon19 deletion (del) or L858R and no CNS metastasis. Randomized
(1:1) pts received ERL (150mg/day) +RAM (10mg/kg q2w) or ERL+PL,
stratied by gender, geographic region (East Asia vs other), EGFRm type
(Ex19del vs L858R) and EGFR testing method. Primary endpoint was
investigator-assessed progression free survival (PFS). Other objectives:
overall response rate (ORR), duration of response (DoR), PFS2, overall
survival (OS), safety and plasma T790M mutation.
Results: 449 pts were randomized. Baseline characteristics were balanced
between treatment arms: Asian 77%, Females 63%, Ex19del 54%. PFS was
signicantly prolonged in the RAM-ERL vs PL-ERL group (medians 19.4
months [mos; 95%CI 15.4, 21.6] vs 12.4 mos [95%CI 11.0, 13.5], strati-
ed hazard ratio [HR] .591; 95%CI .461, .760; p<.0001). ORR was similar
between groups (76.3% [95%CI 70.8, 81.9] vs 74.7% [95%CI 69.0, 80.3]).
DOR was longer for pts responding in the RAM-ERL group (medians,
18.0 mos [95%CI 13.9, 19.8] vs 11.1 mos [95%CI 9.7, 12.3], unstratied
HR .619; 95%CI .477, .805; p=.0003); OS data were immature (82% cen-
soring, medians not reached [NR], HR .832 [.532-1.303]; p=.4209). PFS2
favored RAM-ERL (69% censoring rate, medians NR, HR .690, 95%CI
.490, .972; p=.0325). Grade≥3 treatment-emergent adverse events were
greater with RAM (72%) vs PL (54%), largely driven by hypertension (24
vs 5%, no Grade 4), with 1 treatment related on study death (hemothorax)
in RAM vs 0 PL. EGFR T790M+rates at progression are forthcoming.
Conclusions: RAM+ERL led to superior PFS in 1L EGFRm metastatic
NSCLC. Safety was consistent with the established safety proles of the
individual compounds.
Disclosure Statement: ©2019 ASCO, Inc. Reused with permission. Abstract was
accepted and previously presented at 2019 ASCO-55th Annual Meeting. All rights
reserved.
276
NAB-Paclitaxel Plus Carboplatin As First-Line Therapy for
Patients with Advanced NSCLC in the Real-World Setting:
Safety Results of the Non-Interventional Neptun Study
Tobias Dechow 1; Jorge Riera-Knorrenschild 2; Björn Hackanson 3;
Ludwig Fischer von Weikersthal 4; Marco Chiabudini 5; Barbara Timm 5;
Ralf Michael Zerbes 5; Karin Pottho 5
1Onkologie Hämatologie Ravensburg, Ravensburg, Deutschland
2Universitätsklinikum Gießen und Marburg GmbH, Marburg, Deutschland
3Universitätsklinikum Augsburg, Augsburg, Deutschland
4Gesundheitszentrum St. Marien GmbH, Amberg, Deutschland
5iOMEDICO AG, Freiburg im Breisgau, Deutschland
Purpose: In patients with non-small cell lung cancer (NSCLC), the
combination of nab-paclitaxel plus carboplatin is a standard rst-line
regimen. e favorable ecacy and safety prole of this combination has
been shown in a pivotal phase 3 trial and was conrmed for various patient
subpopulations in the consecutive ABOUND studies. e prospective
non-interventional study NEPTUN was designed to analyze eectiveness,
safety and tolerability of this regimen in the real-world setting in Germany.
Methods: In total, 400 patients with stage IIIB/IV NSCLC scheduled to
receive nab-paclitaxel and carboplatin as rst-line therapy were planned
to be recruited in 100 outpatient centers and hospitals across Germany.
Primary endpoint was the six-month progression-free survival rate. Key
secondary endpoints included further eectiveness parameters, safety and
quality of life (QoL). Descriptive statistics were used to analyze data. e
second interim analysis of the NEPTUN study was scheduled to analyze
eectiveness and safety data as well as QoL. Here, we will focus primarily
on the safety results.
Results: Between 08/2016 and 06/2019 408 patients have been enrolled at
74 active sites. Baseline patient and tumor characteristics including age,
ECOG, co-morbidities, histology, and treatment details including dose
modications and reasons will be presented. Safety and tolerability data
will be analyzed including incidence of (severe) adverse events, adverse
drug reactions and use of supportive care.
Conclusions: e NEPTUN study demonstrates an acceptable safety pro-
le of nab-paclitaxel and carboplatin in patients with advanced NSCLC in
a real-world setting. Toxicity is generally mild and manageable, support-
ing the use of this regimen as a rst-line treatment option.
297
Single-ARM Phase II-STUDY in Patients with Extensive Stage
Small-Cell Lung Cancer (ES-SCLC) with Poor Performance
Status Receiving atezolizumab-Carboplatin-Etoposide (Space;
AIO-TRK-0119)
Jan Stratmann 1; Martin Sebastian 1; Martin Reck 2
1Universitätsklinikum Frankfurt, Medizinische Klinik 2: Hämatologie / Onkologie,
Frankfurt am Main, Deutschland
2LungenClinic Großhansdorf, Großhansdorf, Deutschland
Purpose: Small-cell lung cancer (SCLC) is an aggressive tumor with an
unfavorable prognosis that accounts for approximately 15% of all lung
cancers. Two in three patients (pts) diagnosed with SCLC have metasta-
ses (extensive disease, ED) at primary diagnosis. Platinum-based doublet
chemotherapy has been the palliative standard of care in these pts for over
30 years13.
Addition of the PD-L1-antibody atezolizumab results in a signicant and
meaningful OS benet in patients with ED-SCLC, as shown in the IM-
power133 trial4. e trial excluded pts with low performance status, that
account for approximately one-third of all SCLC pts; therefore, to date no
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data is available regarding safety and ecacy of the triplet combination in
this population.
e SPACE study plans to include 70 pts with low performance status to
provide a reasonable estimate of the primary study endpoint of the 1-year
survival rate; secondary endpoints are response rate, progression-free sur-
vival, safety and quality of life.
Methods: Treatment naive pts with ECOG=2 will receive induction treat-
ment consisting of four 21-day cycles of carboplatin (AUC of 5 mg/mL/
min, IV, d1) and etoposide (cumulative total dose of ≥300 mg/m², IV on
3 consecutive days) with atezolizumab (1200 mg IV, d1), followed by a
maintenance phase during which pts receive atezolizumab (Q3W) until
the occurrence of unacceptable toxicity, disease progression or withdraw-
al of consent or death.
Results: Recruitment not yet started.
References:
1. Griesinger, F, et al. Lungenkarzinom, kleinzellig (SCLC) — Onkopedia.
2. Evans WK, et al. VP-16 and cisplatin as rst-line therapy for small-cell lung
cancer. J Clin Oncol, 1985
3. atcher and Lind, Carboplatin in small cell lung cancer. Semin Oncol. 1990
Feb;17(1 Suppl 2):40-8.
4. Horn L, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage
Small-Cell Lung Cancer. NEJM. 2018;379(23):2220–2229. doi:10.1056/NEJ-
Moa1809064.
Disclosure Statement: SPACE (EudraCT 2019-001707-21) study sponsor is
AIO-Studien-gGmbH; Berlin. e study is nancially supported by F. Hofmann-la
Roche.
301
Neoadjuvant Immune Checkpoint Inhibition in Resectable
Lung Cancer
Thorsten Walles 1; Eva Lücke 2; Christine Ganzert 2; Peter Hass 3;
Michael Kreißl 4; Johannes Haybäck 5; Jens Schreiber 2
1Abteilung Thoraxchirurgie, Universitätsmedizin Magdeburg, Magdeburg
2Klinik für Pneumologie, Universitätsmedizin Magdeburg, Magdeburg
3Klinik für Strahlentherapie, Universitätsmedizin Magdeburg, Magdeburg
4Klinik für Nuklearmedizin, Universitätsmedizin Magdeburg, Magdeburg
5Institut für Pathologie, Universitätsmedizin Magdeburg, Magdeburg
Purpose: Pharmacological inhibition of programmed cell death (PD-1)
protein improves survival in patients with advanced non-small-cell lung
cancer (NSCLC) [1]. e clinical eect of neoadjuvant immune check-
point inhibition (ICI) in patients with resectable or oligometastatic dis-
ease is scarcely explored.
Methods: Retrospective single-center cohort analysis. Tissue biopsies of
NSCLC in advanced stage were tested for PD-L1 expression. In patients
with PD-L1 expression > 50%, ICI were administered before surgery with
surgery planned approximately 4 weeks aer the rst dose. Clinical toler-
ance, radiological and histological tumor response and oncological out-
come were analyzed.
Results: Between 2017 and 2019 four patients (2 male, 2 female; age 56-78
years) received ICI before tumor resection. Tumor histology was adeno
carcinoma in 3 and squamous cell carcinoma in 1 case. All patients had
locally advanced tumors T3 or T4. Mediastinal lymph nodes were positive
in 3 cases. In one patient, a single brain metastasis was present that was
treated by radiotherapy. All patients received at least 2 cycles ICI before
surgery (Pembrolizumab in 3 cases, Atezolizumab in 1 case). ICI therapy
was well tolerated and did not delay surgery. According to RECIST crite-
ria, 3 tumors showed partial remission and 1 patient progressive disease.
All tumors were resected completely. Pathological workup of the surgical
specimen conrmed complete pathologic response (CPR) in 2 and partial
pathologic response (PPR) in 2 cases. Mean follow up is 12 months (1-24).
PPR patients developed either distant metastasis aer 6 months or local
recurrence aer 4 months.
Conclusions: ICI is well tolerated in the neoadjuvant setting for NSCLC
and may induce total tumor remission in selected patients. erapy does
not interfere with surgery and is well tolerated by patients. Prognosis is
very promising in CPR and limited in PPR.
Reference:
1. Forde PM, Cha JE, Smith KN et al. Neoadjuvant PD-1 Blockade in Resectable
Lung Cancer. NEJM 2018; 378: 1976-1986.
Disclosure Statement: e authors declare no conict of interest.
374
Non-Invasive Molecular Proling for Therapy Monitoring
of ALK+ Lung Cancer
Steen Dietz 1, 2; Petros Christopoulos 2, 3; Lisa Gu 1, 2; Volker Endris 4;
Zhao Yuan 5; Simon J. Ogrodnik 1; Tomasz Zemojtel 6; Marc A. Schneider 2, 7;
Anna-Lena Volkmar 4; Michael Meister 2, 7; Thomas Muley 2, 7; Martin Reck 8;
Matthias Schlesner 2, 5; Michael Thomas 2, 3; Albrecht Stenzinger 2, 4, 9;
Holger Sültmann 1, 2
1Division of Cancer Genome Research, German Cancer Research Center (DKFZ),
German Cancer Consortium (DKTK), and National Center for Tumor Diseases
(NCT), Heidelberg, Deutschland
2German Center for Lung Research (DZL), TLRC Heidelberg, Heidelberg,
Deutschland
3Department of Oncology, Thoraxklinik at University Hospital Heidelberg,
Heidelberg, Deutschland
4Institute of Pathology at University Hospital Heidelberg, Heidelberg,
Deutschland
5Bioinformatics and Omics Data Analytics, German Cancer Research Center
(DKFZ), Heidelberg, Deutschland
6Berlin Institute of Health (BIH) Genomics Core Facility, Charité University
Medical Center, Berlin, Deutschland
7Translational Research Unit, Thoraxklinik at University Hospital Heidelberg,
Heidelberg, Deutschland
8Lung Clinic Grosshansdorf, Airway Research Center North, German Center for
Lung Research (DZL), Großhansdorf, Deutschland
9German Cancer Consortium (DKTK), Heidelberg, Deutschland
Purpose: Non-small cell lung cancer (NSCLC) patients with ALK rear-
rangements are routinely treated with tyrosine kinase inhibitors (TKIs),
leading to improved survival. However, clinical courses vary widely as the
tumors inevitably develop resistance. us, early detection and molecular
characterization of treatment failure is important for patient outcome.
Methods: To identify indicators of therapy response and progression,
we performed an analysis of circulating tumor DNA (ctDNA) from
serial plasma samples (n=278) of 73 NSCLC patients with ALK
rearrangements. Using targeted sequencing and shallow whole genome
sequencing (sWGS), we achieved mean unique coverages of >4000x and
0.5x, respectively.
Results: Variable mutation levels were marked in all patients and correlat-
ed with clinical features. For example, mutant ctDNA levels were low in
cases of stable disease, but increased at the time of TKI failure. Targeted
sequencing identied known and novel mutations indicating TKI resis-
tance. We also found mutated TP53 at the time of progression in patients
with initially TP53 wildtype tumors. e progression-free survival of pa-
tients with acquired TP53 mutations was comparable to that of primarily
TP53 mutated and shorter than that of persistently TP53 wildtype cases.
sWGS of ctDNA identied copy number variations, some of which might
contribute to tumor progression. We also measured miRNA abundanc-
es in corresponding serum samples and noted uctuating miRNA levels
during therapy that correlated with the clinical course in several cases.
Conclusions: Our data suggest that liquid biopsies can improve ALK+
NSCLC patient care through early detection of progression and tailored
treatment of resistant tumors. ctDNA and miRNA can indicate the need
to switch treatment and provide information to guide the next-line thera-
py. Detection of acquired TP53 mutations in liquid rebiopsies at the time
of disease progression identies additional high-risk cases and suggests
potential clinical utility of ctDNA monitoring for this disease beyond pro-
ling of ALK resistance mutations.
Conicts of Interest:
SD reports speaker’s honoraria from Roche;
PC reports research funding from Novartis, Roche, AstraZeneca and Takeda as
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts114
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well as advisory board and/or lecture fees from Boehringer, Pzer and Chugai;
AV reports speaker’s honoraria from Astra Zeneca;
VE reports advisory board and lecture fees from AstraZeneca and ermoFisher;
MT reports advisory board honoraria from Novartis, Lilly, BMS, MSD, Roche,
Celgene, Takeda, AbbVie, Boehringer, speaker’s honoraria from Lilly, MSD,
Takeda, research funding from AstraZeneca, BMS, Celgene, Novartis, Roche and
travel grants from BMS, MSD, Novartis, Boehringer;
AS reports advisory board honoraria from BMS, Bayer, AstraZeneca, ermoFish-
er, Novartis, Seattle Genomics speaker’s honoraria from BMS, Bayer, Illumina,
AstraZeneca, Novartis, ermoFisher, MSD, Roche, as well as research funding
from Chugai, Bayer and BMS;
HS reports advisory board and speaker’s honoraria from Roche.
393
Patients with Metastatic Non-Small Cell Lung Cancer and
Targetable Molecular Alterations in Germany. Treatment and
First Outcome Data from The Prospective German Registry
Platform Crisp (AIO-TRK-0315)
Frank Griesinger 1; Wilfried E E Eberhardt 2; Arnd Nusch 3; Marcel Reiser 4;
Mark-Oliver Zahn 5; Norbert Marschner 6; Martina Jänicke 7; Annette
Fleitz 7; Lisa Spring 7; Jörg Sahlmann 7; Aysun Karatas 8; Annette Hipper 8;
Wilko Weichert 9; Cornelius F Waller 10; Martin Reck 11;
Petros Christopoulos 12; Martin Sebastian 13; Michael Thomas 12
1Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Deutschland
2Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, Ruhrlandklinik, University Duisburg-Essen, Essen, Deutschland
3Praxis für Hämatologie und internistische Onkologie, Ratingen, Deutschland
4PIOH - Praxis Internistischer Onkologie und Hämatologie, Köln, Deutschland
5Überörtliche Berufsgemeinschaft MVZ Onkologische Kooperation Harz, Goslar,
Deutschland
6Praxis für Interdisziplinäre Onkologie und Hämatologie, Freiburg, Deutschland
7iOMEDICO Freiburg, Freiburg, Deutschland
8AIO-Studien-gGmbH, Berlin, Deutschland
9Technical University of Munich, Institute of Pathology, München, Deutschland
10Universitätsklinikum Freiburg Innere Medizin I, Freiburg, Deutschland
11LungenClinic, Airway Research Center North (ARCN), German Center for Lung
Research (DZL), Grosshansdorf, Deutschland
12Internistische Onkologie der Thoraxtumoren, Thoraxklinik im
Universitätsklinikum Heidelberg, Translational Lung Research Center
Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL),
Heidelberg, Deutschland
13University Hospital Frankfurt, Frankfurt a.M., Deutschland
Purpose: Guidelines for stage IV NSCLC recommend stratied treatment
by biomarker test results. We used CRISP to evaluate treatment and out-
come of patients (pts) with targetable molecular alterations.
Methods: Currently 163 sites in Germany have recruited >4255 pts at start
of 1st-line who will be followed until death or end of project. Data from
2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed.
Progression-free survival (PFS) was determined in pts observed ≥1 year
(recruited <06/2017 (n=906), outcome sample (ous)).
Results: 94%/65% of 1732/472 pts with non-squamous/squamous tu-
mors were tested for any biomarker. In 2018 test rate was 96%/75% and
49%/33% were tested for all biomarkers (EGFR, ALK, ROS1, BRAF) with
approved targeted therapies (aTT). An alteration in EGFR, ALK, ROS1
or BRAF was detected in 9%, 3%, 2%, and 2% of pts, respectively. Of pts
with druggable EGFR mutation (EGFR+ pts, n=149) 78% received EG-
FR-aTT in 1st-line. In 2nd-line, 20% received EGFR-aTT, 15% something
else, 11% died prior to 2nd-line, 54% were still in 1st-line. Median PFS of
EGFR+ pts was 7.1 months (n = 67, 61% events, 95%-CI 5.2-10.1), in total
46% (n=31) of pts had died (ous). Of pts with druggable ALK alteration
(n=55), 47% received ALK-aTT in 1st-line. In 2nd-line, 22% received ALK-
aTT, 11% something else, 13% died prior to 2nd-line, 54% were still in 1st-
line. In the ous (n=29), 55% (n=16) of tumors had already progressed, in
total 24% (n=7) of pts had died. All 6 pts with druggable ROS1 alteration
received chemotherapy, while 6 of the 9 pts with druggable BRAF muta-
tion and start of treatment in 2017/18 received a BRAF-ATT in 1st-line.
Conclusions: Pts are frequently tested for molecular alterations. While
EGFR-aTT is well established as 1st-line and rst data are promising for
BRAF-aTT, pts with ALK/ROS alteration are not routinely treated with
1st-line aTT, reasons are not yet clear.
Disclosure Statement: None of the authors has declared a conict of interest
regarding the subject of this work.
394
Patients with Metastatic Non-Small Cell Lung Cancer and
PD-L1 Expression in Germany. Treatment and First Outcome
from the Prospective German Registry Platform Crisp
(AIO-TRK-0315)
Martin Sebastian 1; Wilfried E E Eberhardt 2; Christoph Losem 3;
Christiane Bernhardt 4; Christoph Maintz 5; Norbert Marschner 6;
Martina Jänicke 7; Annette Fleitz 7; Lisa Spring 7; Jörg Sahlmann 7;
Aysun Karatas 8; Annette Hipper 8; Wilko Weichert 9; Petra Hoknecht 10;
Christian Grah 11; Achim Rittmeyer 12; Frank Griesinger 13; Michael Thomas 14
1University Hospital Frankfurt, Frankfurt a.M., Deutschland
2Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, Ruhrlandklinik, University Duisburg-Essen, Essen, Deutschland
3MVZ für Onkologie und Hämatologie im Rhein-Kreis Neuss, Neuss,
Deutschland
4Gemeinschaftspraxis für Hämatologie und Onkologie Dortmund, Dortmund,
Deutschland
5MVZ West GmbH Würselen Hämatologie-Onkologie, Würselen, Deutschland
6Praxis für Interdisziplinäre Onkologie und Hämatologie, Freiburg, Deutschland
7iOMEDICO Freiburg, Freiburg, Deutschland
8AIO-Studien-gGmbH, Berlin, Deutschland
9Technical University of Munich, Institute of Pathology, München, Deutschland
10Niels-Stensen-Kliniken Franziskus-Hospital Harderberg, Georgsmarienhütte,
Deutschland
11Gemeinschaftskrankenhaus Havelhöhe gGmbH, Berlin, Deutschland
12Lungenfachklinik Immenhausen, Immenhausen, Deutschland
13Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Deutschland
14Internistische Onkologie der Thoraxtumoren, Thoraxklinik im
Universitätsklinikum Heidelberg, Translational Lung Research Center
Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL),
Heidelberg, Deutschland
Purpose: Treatment guidelines for stage IV NSCLC recommend strati-
ed treatment according to biomarker testing results. We used CRISP to
evaluate treatment and outcome of patients (pts) with PD-L1-expressing
tumors.
Methods: Currently 163 centers in Germany have recruited over 4255 pts
at start of 1st-line who will be followed until death or end of project. Data
from 2204 pts recruited by 133 centers between 12/2015 and 06/ 2018
was analyzed regarding PD-L1 testing, treatment and outcome. Progres-
sion-free survival (PFS) was determined in patients being ≥1 year under
observation (recruited until June 30th 2017 (n=906), outcome sample,
(ous)).
Results: Test rates for PD-L1 increased from 25% (2016) to 75% (2018) in
pts with non-squamous tumors (n=1732), and from 20% (2016) to 62%
(2018) in pts with squamous tumors (n=472). PD-L1 TPS was ≥50% in
16% of pts, 1-49% in 18% of pts, and <1% in 7% of pts, while 3%/12% of
pts were classied by pathologists as PD-L1 positive/negative with TPS
not specied. In 9% and 4% an EGFR or ALK alteration was also detected,
respectively.
Of all pts with PD-L1 TPS≥50% 70% received pembrolizumab-based 1st-
line treatment, 21% chemotherapy and 9% another/targeted therapy. At
database cut, 20% had started 2nd-line, 19% had died prior to a 2nd-line
and remaining pts were still in 1st-line. In the ous, median PFS of all pts
with PD-L1 positive tumors was 4.4 months (62% events, 95%-CI 3.5-5.5
months, n=185), in pts with PD-L1 TPS≥50% (n=83) so far 53% had a
progression aer 1st-line. In total, 49% of pts with PD-L1 positive tumors
and 41% of pts with PD-L1 TPS≥50% had died (ous).
Conclusions: Testing for PD-L1 has been quickly integrated into routine
care diagnostics. e majority of pts with PD-L1 positive tumors and a
TPS≥50% receive an immune-oncology therapy. e impact of these
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 115
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novel targeted treatment approaches on the outcome of pts will be subject
of future analyses.
Disclosure Statement: None of the authors has declared a conict of interest
regarding the subject of this work.
395
Patients with Metastatic Non-Small Cell Lung Cancer without
Molecular Alterations or PD-L1 Expression in Germany.
Treatment and First Outcome from The Prospective German
Registry Platform Crisp (AIO-TRK-0315)
Frank Griesinger 1; Wilfried E E Eberhardt 2; Harald-Robert Bruch 3;
Jacqueline Rauh 4; Eyck von der Heyde 5; Norbert Marschner 6;
Martina Jänicke 7; Annette Fleitz 7; Lisa Spring 7; Jörg Sahlmann 7;
Aysun Karatas 8; Annette Hipper 8; Wilko Weichert 9; Parvis Sadjadian 10;
Martin Metzenmacher 11; Wolfgang Gleiber 12; Martin Sebastian 12;
Michael Thomas 13
1Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Deutschland
2Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, Ruhrlandklinik, University Duisburg-Essen, Essen, Deutschland
3Praxiskooperation Bonn-Euskirchen, Bonn, Deutschland
4GIM - Gemeinschaftspraxis Innere Medizin, Witten, Deutschland
5Onkologische Schwerpunktpraxis Hannover, Hannover, Deutschland
6Praxis für Interdisziplinäre Onkologie und Hämatologie, Freiburg, Deutschland
7iOMEDICO Freiburg, Freiburg, Deutschland
8AIO-Studien-gGmbH, Berlin, Deutschland
9Technical University of Munich, Institute of Pathology, München, Deutschland
10Johannes Wesling Klinikum Minden, Minden, Deutschland
11Universitätsklinikum Essen (AöR), Essen, Deutschland
12University Hospital Frankfurt, Frankfurt a.M., Deutschland
13Internistische Onkologie der Thoraxtumoren, Thoraxklinik im
Universitätsklinikum Heidelberg, Translational Lung Research Center
Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL),
Heidelberg, Deutschland
Purpose: Guidelines for stage IV NSCLC recommend stratied treatment
by biomarker test results. We used CRISP to evaluate treatment and out-
come of patients (pts) in whom neither targetable molecular alterations
nor any PD-L1 expression were detected.
Methods: Currently 163 sites in Germany have recruited >4255 pts at start
of 1st-line who will be followed until death or end of project. Data from
2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed.
ese pts started treatment prior approval of immune checkpoint inhibi-
tors (ICI) for this group of pts. Progression-free survival (PFS) was deter-
mined in pts ≥1 year under observation (recruited until 06/2017 (n=906),
outcome sample (ous)).
Results: 6% of pts with non-squamous (nsq) and 35% with squamous (sq)
tumors received no type of biomarker testing prior to start of 1st-line, and
in 49% and 36% no targetable alterations or any PD-L1 expression were
detected. us, 55% and 71% of pts (nsq/sq) were eligible for chemother-
apy (ctx) but no type of targeted therapy at start of 1st-line.
In 1st-line, pts received carboplatin- (55%) or cisplatin-based ctx (24%),
13% targeted therapy (e.g. ICI in trial, switch to TKI but test result not yet
documented).
At database cut, 33% of all pts had started 2nd-line, 24% had died prior to a
2nd-line and remaining pts were still in 1st-line. In the ous, median PFS was
5.0 months (66% events, 95%-CI 4.5-5.5 months, n=457) for nsq tumors
and 4.5 months (66% events, 95%-CI 3.4-5.3 months, n=154) for sq tu-
mors. In total 55% of pts with nsq and 53% of pts with sq tumors had died.
Conclusions: Despite break-throughs with targeted therapies and high
test rates in routine care, the majority of pts do not qualify for targeted
therapy. First outcome results indicate that prognosis is poor in these pts.
Outcome will hopefully improve in the cohort now treated with ctx-ICI
combination.
Disclosure Statement: None of the authors has declared a conict of interest
regarding the subject of this work.
399
Caspian: Os Results from a Randomised Phase 3 Study
of First-Line Durvalumab ± Tremelimumab + Chemotherapy
in ES-SCLC
Niels Reinmuth 1; Luis Paz-Ares 2; Yuanbin Chen 3; Katsuyuki Hotta 4;
Dmytro Trukhin 5; Galina Statsenko 6; Maximilian J Hochmair 7;
Mustafa Özgüroğlu 8; Jun Ho LI 9; Oleksandr Voitko 10; Artem Poltoratskiy 11;
Santiago Ponce 12; Francesco Verderame 13; Libor Havel 14;
Igor Bondarenko 15; Andrzej Kazarnowicz 16; György Losonczy 17;
Nicolay V Conev 18; Jon Armstrong 19; Natalie Byrne 19; Norah Shire 19;
Haiyi Jiang 19; Jonathan Goldman 20; Jürgen Alt 21
1Asklepios Fachkliniken München-Gauting, Gauting, Deutschland
2Hospital Doce de Octubre, Medical Oncology Department , Madrid, Spanien
3Cancer and hematology centers of western Michigan - Muskegon, Norton
Shores, United States
4Okayama University Hospital, Center for Innovative Clinical Medicine,
Okayama, Japan
5Municipal Institution Odessa Regional Oncology Dispensary, unit of
dispensary-polyclinic department, Odesa, Odes’ka oblast, Ukraine
61st Hospital City Clinical, Novosibirsk, Russland
7Otto-Wagner-Spital, Wien, Österreich
8University-Cerrahpaşa, Cerrahpaşa School of Medicine, Fatih/Istanbul, Turkey
9Changwon Samsung Medical Center, Division of Hemato-Oncology,
Department of Internal Medicine, Changwon, Südkorea
10Kyiv City Oncology Hospital, Kyiv, Ukraine
11N. N. Petrov Institute of Oncology, St Petersburg, Russland
12Hospital Universitario 12 de Octubre, Medical Oncology, Madrid, Spanien
13Humanitas Catanese Center of Oncology, Catania, Italien
14Thomayer’s Hospital, 1st Faculty of Medicine of Charles University,
Prague, Tschechien
15Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine
16Tuberculosis and Lung Disease Hospital, Olsztyn, Poland
17Complejo Hospitalario Universitario A Coruña, Coruno, Spanien
18Medical University of Varna, Varna, Bulgaria
19AstraZeneca, Gaithersburg, United States
20University of California, Los Angeles, United States
21Universitätsklinikum Mainz, III. Medizinische Klinik und Poliklinik, Mainz,
Deutschland
Purpose: Immune checkpoint blockade targeting the PD-1/PD-L1 pathway
in combination with platinum-based chemotherapy (CT) has demonstrated
improved clinical outcomes in patients (pts) with extensive-stage small-cell
lung cancer (ES-SCLC). Treatment with durvalumab (D), a selective, high-af-
nity, human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, and
tremelimumab (T), a selective human IgG2 mAb against CTLA-4, may pro-
vide possible additive or synergistic eects. Durvalumab demonstrated dura-
ble clinical activity and had a manageable safety prole both as monothera-
py and in combination with tremelimumab in pts with pretreated ES-SCLC
(NCT01693562; NCT02261220; NCT02937818). CASPIAN (NCT03043872)
is a randomised, multicentre, open-label, sponsor-blind, Phase 3 study of
Durvalumab ± Tremelimumab in combination with etoposide and plati-
num-based CT (EP) as rst-line treatment for pts with ES-SCLC.
Methods: In total, 804 pts were randomised 1:1:1 to receive D 1500 mg +
T 75 mg + EP q3w for 4 cycles, followed by D 1500 mg q4w until disease
progression (PD), with one additional dose of T given post EP (Arm 1); D
1500 mg + EP q3w for 4 cycles, followed by D 1500 mg q4w until PD (Arm
2); or EP q3w for 4–6 cycles with prophylactic cranial irradiation if indicat-
ed (Arm 3). Randomisation was stratied by platinum-based CT in cycle 1
(carboplatin vs cisplatin). Pts had histologically or cytologically document-
ed ES-SCLC, WHO/ECOG PS 0 or 1 and were suitable to receive rst-line
platinum-based CT. e primary endpoint was overall survival (OS) for D
± T + EP versus EP. Secondary endpoints included progression-free sur-
vival (PFS); objective response rate; landmark OS and PFS rates; safety and
tolerability; pharmacokinetics; immunogenicity; quality of life.
Results: Results will be presented at WCLC 2019 including OS, key sec-
ondary endpoints, safety and tolerability.
Conclusions: Not applicable.
Reference:
1. Paz-Ares, L. et al., WCLC 2019, Barcelona, #2265
Disclosure Statement: Funding by AstraZeneca
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2018
409
Clinical and Molecular Predictors for The Development
ofEGFR T790M at Failure of First- or Second-Generation
EGFR Inihibitors
Petros Christopoulos 1, 2; Anna-Lena Volckmar 3; Farastuk Bozorgmehr 2, 4;
Nikolaus Magios 4; Jonas Kuon 4; Martina Kirchner 3; Daniel Kazdal 3;
Volker Endris 3; Tilmann Bochtler 4; Felix Herth 2, 4; Claus-Peter Heussel 2, 4;
Hauke Winter 2, 4; Thomas Muley 2, 4; Michael Meister 2, 4; Stefan Rieken 5;
Jürgen R. Fischer 6; Martin Faehling 7; Helge G. Bischo 4;
Albrecht Stenzinger 2, 3; Michael Thomas 2, 4
1Thoraxklinik-Heidelberg gGmbH, Heidelberg, Deutschland
2Translational Lung Research Center Heidelberg, member of the German Center
for Lung Research (DZL)
3Institute of Pathology Heidelberg, Heidelberg, Deutschland
4Thoraxklinik-Heidelberg gGmbH, Heidelberg, Deutschland
5Radioonkologie und Strahlentherapie, Heidelberg, Deutschland
6Onkologie / Krebsheilkunde mit Palliativmedizin, Lungenklinik Loewenstein,
Löwenstein, Deutschland
7Klinik für Kardiologie, Angiologie, Pneumologie, Klinikum Esslingen, Esslingen,
Deutschland
Purpose: Approximately half of epidermal growth factor receptor
(EGFR)+ non-small cell lung cancer (NSCLC) patients failing rst- or sec-
ond-generation EGFR inhibitors (TKI) feature EGFR T790M mutations
and sensitivity to osimertinib, but it is unclear at present which factors
determine this constellation.
Methods: We retrospectively analyzed EGFR+ NSCLC patients that un-
derwent T790M testing at the time of TKI failure at our institutions.
Results: EGFR T790M testing was performed for 182 cases using liquid
biopsies (n=53), tissue rebiopsies (n=110) or both (n=19). Median age
was 64 years with a predominance of female (65%) never-/light-smok-
ers (69%). A positive T790M result was noted in 101/182 patients (55%)
and followed by treatment with osimertinib in 75/101, resulting in a sig-
nicantly longer overall survival (52 vs. 30 months from start of rst-line
treatment, logrank p=0.001). Detection of T790M was positively associ-
ated with presence of EGFR exon 19 deletions (67% vs. 35% in del19+ vs.
del19- cases, p<0.001), and negatively associated with EGFR L858R (48%
vs. 65%, p=0.047), “rareEGFR mutations (18% vs. 60%, p=0.001) and
presence of co-mutations at baseline in the 38-42 genes covered by our
NGS panel, including TP53 (42% vs. 58%, p=0.042). No signicant re-
lationship was noted with patient sex, age, smoking status, initial ECOG
performance status, histology, previous nonmetastatic NSCLC, pattern
of metastatic spread, lymphocyte-to-neutrophil ratio, use of palliative ra-
diotherapy or surgery, but T790M+ cases were slightly enriched among
patients with rst-line TKI treatment duration > 1 year (63% vs. 48%,
p=0.035).
Conclusions: Acquired EGFR T790M mutations under rst- or sec-
ond-generation EGFR inihibitors are an important prognostic factor with
major therapeutic relevance, but their development cannot be reliably
predicted at present. eir associations with the type of EGFR mutation
and presence of co-mutations suggest that deeper molecular proling
might facilitate identication of more accurate biomarkers.
411
Osimertinib vs Comparator EGFR-TKI As First-Line Treatment
for EGFRM Advanced NSCLC (Flaura): Final Overall Survival
Analysis
Niels Reinmuth 1; Helge Bischo 2; Sabine Bohnet 3;
Christian Meyer Zum Büschenfelde 4; Antje Rückert 5; Rachel Hodge 6;
Yuri Rukazenkov 6; Suresh S. Ramalingam 7
1Asklepios Fachkliniken München-Gauting, Gauting, Deutschland
2Thoraxklinik Heidelberg gGmbH, Heidelberg, Deutschland
3Universitätsklinikum Schleswig‐Holstein, Campus Lübeck, Medizinische
Klinik III - Pulmologie, Lübeck, Deutschland
4St. Vincentius‐Kliniken Karlsruhe, Karlsruhe, Deutschland
5Schwarzwald‐Baar Klinikum Villingen‐Schwenningen GmbH, Villingen‐
Schwenningen, Deutschland
6AstraZeneca, Cambridge, United Kingdom
7Emory University, WinshipCancer Institute, Atlanta, United States
Purpose: Osimertinib, a 3rd generation, irreversible, oral EGFR-TKI po-
tently and selectively inhibits both EGFRm and EGFR T790M and has
demonstrated ecacy in NSCLC CNS metastases. e phase III FLAURA
study (NCT02296125) compared 1st line osimertinib vs comparator EG-
FR-TKI in EGFRm advanced NSCLC. Median progression-free survival
(PFS; primary analysis, DCO 06/12/2017) was signicantly longer with
osimertinib than comparator EGFR-TKI (18.9 vs 10.2 months; p<0.001).
Overall survival (OS) data were immature (25% maturity) at the time of
the primary publication.
Methods: Patients (pts; 556 globally) were randomised 1:1 to osimerti-
nib 80 mg once daily (qd) orally (po) or comparator EGFR-TKI (getinib
250 mg qd or erlotinib 150 mg qd po) and stratied by race (Asian/non-
Asian) and mutation status (Ex19del/L858R). Inclusion criteria: ≥18 years
(Japan: ≥20); treatment-naïve with Ex19del/L858R EGFRm advanced
NSCLC; WHO PS 0–1; neurologically stable pts with CNS metastases
were allowed, provided denitive treatment/steroids were completed for
≥2 weeks. Treatment beyond progression (RECIST 1.1, per investigator)
was allowed if clinical benet continued; pts randomised to the compara-
tor arm could crossover to osimertinib if T790M positive on progression
(BICR conrmed). Primary endpoint: PFS by RECIST 1.1, per investiga-
tor. OS is a secondary endpoint. Safety and tolerability measures included
adverse events (CTCAE v4), clinical and physical assessments.
Results: e data for nal OS analysis (app. 60% maturity across both
arms) is anticipated by 08/2019. At ESMO 2019 median OS, 2- and 3- year
survival rates will be reported for each arm as well as OS across predened
subgroups including race and EGFR mutation type as well as updated
safety data. We will for the rst time provide FLAURA data on the prev-
alence of T790M mutations in dierent molecular subgroups (Ex19del/
L858R) aer progression on 1st line EGFR-TKI.
Conclusions: Not applicable.
Reference:
1. Ramalingam, SS et al., ESMO 2019, Barcelona, LBA to be submitted
Disclosure Statement: Funding by AstraZeneca
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464
Clinical Characteristics and Outcome of BRAF-Mutated
Advanced NSCLC in Two Large German Lung Cancer Centers
Cedric Preuß 1; Julia Roeper 2, 3; Martin Metzenmacher 1;
Wilfried Eberhardt 1, 4; Ursula Stropiep 3, 5; Katrin Wedeken 3, 5;
Henning Reis 6; Thomas Herold 6; Kaid Darwiche 7; Clemens Aigner 8;
Martin Stuschke 9; Kurt Werner Schmid 6; Markus Falk 3, 10;
Lukas C. Heukamp 3, 10; Markus Tiemann 3, 10; Martin Schuler 1, 4, 11;
Marcel Wiesweg 1, 4; Frank Griesinger 3, 5
1Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum,
Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Deutschland
2Innere Medizin-Onkologie, Universitätsmedizin Oldenburg, Pius-Hospital,
Oldenburg, Deutschland
3Lungennetzwerk NOWEL, Oldenburg, Deutschland
4Thorakale Onkologie, Westdeutsches Lungenzentrum, Ruhrlandklinik -
Universitätsmedizin Essen, Universität Duisburg-Essen, Essen, Deutschland
5Hämatologie und Onkologie, Innere Medizin-Onkologie, Universitätsmedizin
Oldenburg, Pius-Hospital, Oldenburg, Deutschland
6Institut für Pathologie, Westdeutsches Tumorzentrum, Universitätsklinikum
Essen, Universität Duisburg-Essen, Essen, Deutschland
7Klinik für Pneumologie, Sektion Interventionelle Bronchologie, Westdeutsches
Lungenzentrum, Ruhrlandklinik - Universitätsmedizin Essen, Universität
Duisburg-Essen, Essen, Deutschland
8Thoraxchirurgie und thorakale Endoskopie, Westdeutsches Lungenzentrum,
Ruhrlandklinik - Universitätsmedizin Essen, Universität Duisburg-Essen, Essen,
Deutschland
9Klinik für Strahlentherapie, Westdeutsches Tumorzentrum, Universitätsklinikum
Essen, Universität Duisburg-Essen, Essen, Deutschland
10Institut für Hämatopathologie Hamburg, Hamburg, Deutschland
11Deutsches Konsortium für Translationale Krebsforschung (DKTK), Standort
Essen/Düsseldorf, Deutschland
Purpose: BRAF-mutated non-small cell lung cancer (NSCLC) has been
established as a molecularly dened subentity with specic clinical and
biological characteristics. BRAF mutations can be functionally classied1
(class I: V600x, constitutively active monomer; class II: constitutively ac-
tive dimers; class III: low kinase activity, heterodimers amplifying the RAS
signal). Available kinase inhibitors are eective only for V600x mutations.
Recently, class II/III mutations were associated with adverse prognosis2.
We set out to clinically characterize a cohort of BRAF mutated NSCLC
and compare functional class-specic outcome, including the time before
kinase inhibitors became available.
Methods: Retrospective study in two German lung cancer centers. Pa-
tients were identied by database query and clinical data collected from
the electronic patient charts.
Results: We identied 72 patients (m/f 53/47%, median age 64.7y) di-
agnosed 2010-2019 with advanced NSCLC. Median follow up was 23.9
months. 43% of patients had V600x mutations, 32% class II, 25% class III.
Most patients had a positive smoking history, with a trend towards a high-
er proportion in class II/III patients (81% vs 97%, p=0.1). Only a minority
of patients with V600x mutations received kinase inhibitors (16%), which
have been available only since 2017. Median overall survival (OS) was
13.1 months and diered signicantly compared to a reference control
group of 748 NSCLC patients without BRAF mutations (median OS 22.0
months, HR 1.39, p=0.043). In contrast, median OS upon beginning of
palliative therapy (OSpall) was identical (HR 1.03, p=0.9). In this cohort
with only little inuence of targeted therapy, overall survival by functional
class of the mutation was identical (class I vs. II/III, HR 1.02, p=0.95).
Conclusions: e availability of targeted therapy solely for class I muta-
tions appears to be a major factor contributing to the reported superior
outcome compared to class II/III cohorts.
References:
1. Yao, Z. et al. Nature 548, 234–238 (2017)
2. Dagogo-Jack; I. et al. Clin. Cancer Res. 25; 158–165 (2019)
469
Registrational Results of Libretto-001: a Phase 1/2 Trial of
LOXO-292 in Patients with RET-Fusion-Positive Lung Cancer
Jürgen Wolf
Uniklinik Köln, Innere Medizin I, Köln, Deutschland
Purpose: LOXO-292 is a highly selective RET inhibitor with activity
against RET fusions, activating RET mutations and brain metastases.
Methods: is phase 1/2 study (87 sites, 16 countries) enrolled patients
(pts) with advanced RET-altered solid tumors including RET fusion-pos-
itive (RET+) NSCLC (NCT03157128). LOXO-292 was dosed orally in
28-day cycles. Phase 1 established MTD/RP2D (160mg BID). Phase 2
enrolled pts to 1 of 6 cohorts based on tumor type, RET alteration & pri-
or therapies. Primary endpoint: ORR; secondary endpoints: DoR, CNS
ORR, CNS DoR, PFS, and safety.
Results: As of 17-06-19, 253 RET+ NSCLC pts were treated. Primary
analysis set (PAS): rst 105 consecutively enrolled RET+ NSCLC pts who
received prior platinum-based chemotherapy (PBC); 58 pts also received
prior anti-PD-1/PD-L1 agents. Majority of PAS responders were followed
for ≥6 months (m) from rst response. Of remaining 148 pts, 79 were pre-
viously treated with PBC, 55 did not receive prior PBC & 14 did not have
measurable disease at baseline.
Investigator-assessed ORR in PAS: 68% (95%CI 58-76%, n=71/105, 2 PRs
pending conrmation). Responses did not dier by prior therapy (e.g.
anti-PD-1/PD-L1, multikinase inhibitors). Median DoR: 20.3m (95%CI
13.8-24.0) with median follow-up of 8m; as evidenced by wide CI, DoR
estimate is not statistically stable due to low event number (16/69 con-
rmed responders). Intracranial ORR: 91% (n=10/11:2 conrmed CRs, 8
conrmed PRs) for pts with CNS target lesions at baseline.
ORR in treatment-naïve RET+ NSCLC pts: 85% (95%CI 69-95%, n=29/34,
7 PRs pending conrmation). In safety data set of 531 pts, 5 treatment-re-
lated AEs occurred in ≥15% pts: dry mouth, diarrhea, hypertension,
increased AST & ALT. Most AEs: Gr 1-2. Nine (1.7%) pts discontinued
LOXO-292 for treatment-related AEs.
Conclusions: LOXO-292 had marked antitumor activity in RET+ NSCLC
pts & was well tolerated. ese data will form the basis of an FDA NDA
submission later this year.
Disclosure Statement: Previously presented at WCLC 2019.
Jürgen Wolf is author on behalf of the LIBRETTO-001 Investigators
472
Enlarge-Lung: Two-Year Follow-Up of Real-World Patients with
Locally Advanced or Metastatic (Stage IIIB/IV) Squamous and
Non-Squamous Non-Small Cell Lung Cancer (NSCLC) from a
National, Prospective, Non-Interventional Study (NiS Enlarge)
of Nivolumab after Prior Chemotherapy in Germany
Andreas Gröschel 1; Christian Schumann 2; Sylvia Gütz 3; Holger Schulz 4;
Harald Müller-Huesmann 5; Clemens Schulte 6; Rüdiger Liersch 7;
Eyck von der Heyde 8; Verena Wünsch 9; Martin Sebastian 10
1Klinik für Innere Medizin II - Pneumologie und Beatmungsmedizin,
Clemenshospital, Münster
2Klinikum Kempten, Pneumologie, Thoraxonkologie, Schlaf- und
Beatmungsmedizin, Kempten
3Ev. Diakonissenkrankenhaus GmbH, Zentrum für Innere Medizin, Leipzig
4Praxis Internistischer Onkologie und Hämatologie, pioh, Frechen
5Brüderkrankenhaus St. Josef, Klinik für Hämatologie und Onkologie, Paderborn
6Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund
7Gemeinschaftspraxis für Hämatologie und Onkologie, GEHO, Münster
8Studienzentrum am Raschplatz, Hannover
9Bristol-Myers Squibb GmbH & Co KG aA, München
10Medizinische Klinik II, Abteilung Hämatologie, Medizinische Onkologie,
Universitätsklinikum Frankfurt, Frankfurt
Purpose: In two registrational trials, nivolumab showed overall survival
(OS) benet versus docetaxel in pretreated locally advanced or metastatic
NSCLC. ese results have been conrmed by initial data disclosure of
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the German NIS ENLARGE. Here we report mature OS data from the rst
300 patients enrolled in the trial.
Methods: 882 patients with pretreated, locally advanced or metastatic NS-
CLC recruited from 79 cancer care facilities in Germany will be followed
for a period of 5 years from initiation of nivolumab until death, with-
drawal of consent, loss of follow-up/record or end of study. e prima-
ry endpoint is OS. Baseline characteristics are reported using descriptive
statistics. OS from the time of rst nivolumab dose is estimated using the
Kaplan–Meier method. Study was initiated in July 2016.
Results: With the data cut o on July 31st 2019, interim data of the rst
300 patients from the ENLARGE study describe baseline characteristics
and OS of patients with a minimum follow-up of 25 months. We report
OS and response rates for the total population, by histology and other
subgroups of interest (biomarker, ECOG Performance Status, elderly,
metastases).
Conclusions: Real world data provide complementary information about
special patient populations underrepresented in interventional clinical
trials (elderly; poor performance status; comorbidities) and outcomes of
treatment with nivolumab in accordance with the market authorization
approval in Germany.
484
Real World Molecular Testing in Patients with EGFR Mutation-
Positive (EGFRM+) Locally Advanced or Metastatic NSCLC in
Routine Practice in Germany – Interim Results of The Clinical
Registry Panorama
Wolfgang Schütte 1; Christian Schumann 2; Reinhard Büttner 3;
Karl-Matthias Deppermann 4; Niels Reinmuth 5; Michael Thomas 6;
Mark Wroblewski 7; Frank Griesinger 8
1Martha-Maria Krankenhaus Halle-Dölau gGmbH, Klinik für Innere Medizin II,
Halle (Saale), Deutschland
2Klinikverbund Kempten-Oberallgäu gGmbH, Pneumologie, Thoraxonkologie,
Schlaf- und Beatmungsmedizin, Kempten, Deutschland
3Universitätsklinikum Köln, Institut für Pathologie, Köln, Deutschland
4Sana Kliniken Düsseldorf GmbH, Klinik für Pneumologie, Düsseldorf,
Deutschland
5Asklepios Fachkliniken München-Gauting, Department of Thoracic Oncology,
Gauting, Deutschland
6Thoraxklinik im Universitätsklinikum Heidelberg, Internistische Onkologie der
Thoraxtumoren, Heidelberg, Deutschland
7AstraZeneca GmbH, Oncology, Wedel, Deutschland
8Pius-Hospital Oldenburg, Klinik für Hämatologie und Onkologie, Oldenburg,
Deutschland
Purpose: Epidermal Growth Factor Receptor mutations (EGFRm) are
among the most common in patients (pts) with non-small cell lung can-
cer (NSCLC) and can be targeted with EGFR tyrosine kinase inhibitors
(TKIs). Appr. 50% of the pts will acquire resistance by the T790M muta-
tion (T790M). Osimertinib (OSI) is a 3rd generation TKI and standard of
care for pts who developed the acquired resistance by T790M during the
prior TKI treatments.
Methods: PANORAMA (NCT02777658) is a prospective, clinical registry
for pts with EGFRm+ locally advanced or metastatic NSCLC, who pro-
gressed aer prior TKI therapy. Besides others the 2nd interim analysis
(cut-o: 1APR2019) reects data on routine clinical, molecular testing
using descriptive statistics.
Results: Data of 148 evaluable pts were analysed: At diagnosis median
age was 67.5 yrs (min-max 38.4-84.5 yrs), 49 (33%) pts were male and 98
(66%) were diagnosed with NSCLC Stage IV. 124 pts (84%) were tested
for EGFRm at diagnosis, the remaining pts at later time points. At time
of progression on/aer TKI 74/148 pts were tested again, overall re-test
rate aer progression at any time was 76% (113 pts). 107 (95%) out of
these 113 re-tested pts were tested for T790M thereof 73 pts (64%) were
T790M pos (14 pts not yet documented). 55 (75%) pts who were tested
T790M pos aer progression (n=73) were treated with OSI. No dierence
in T790M positivity in the EGFRm subgroups (Ex19Del, L858R) was ap-
parent. Further details on molecular testing will be shown.
Conclusions: e results will help to understand evolving Real World pts
management, treatment patterns and associated outcomes among pts with
EGFRm locally advanced or metastatic NSCLC who have progressed on/
aer TKI therapy. ese data help validating the growing number of data
sets suggesting that only a minority of EGFRm NSCLC pts benet from
sequential TKI-treatment with OSI aer TKI-progression.
Reference:
1. Schumann, C. et al., DGHO-2019, Berlin, #A-1089-0026-00488
Disclosure Statement: Sponsor AstraZeneca
Christian Schumann: Beratungs‐ bzw. Gutachtertätigkeit & Honorare: AstraZeneca
Reinhard Büttner: Honoraria (alle „minor“); Lectures and Advisory boards for
AbbVie, AstraZeneca, Bayer, Bms, Boehringer‐Ingelheim, Illumina, Lilly, MSD,
Novartis, Qiagen, Pzer, Roche; Firmenanteile: Co‐Founder and Scientic Advisor
for Targos Mol. Pathology Inc; Zulassungsverfahren: Testifying Advisor for MSD
in GBA‐assessment for Pembrolizumab, Advisor for Durvalumab
Karl-Matthias Deppermann: Advisory/Consultancy: AstraZeneca, MSD, Boeh-
ringer, Roche, Takeda; Speaker bureau/Expert testimony: AstraZeneca, MSD,
Boehringer, Roche
Niels Reinmuth: AstraZeneca: Advisory/Consultancy; Speaker bureau/Expert
testimony, Travel/Accommodation/Expenses
Unabhängig vom Abstract habe ich Speaker honoraria / advisories and travel
support erhalten von: Bms, Msd, Roche, Abbvie, Takeda und Böhringer erhalten.
Michael omas: Advisory/Consultancy: AbbVie, BMS, Boehringer, Celgene,
Lilly, MSD, Novartis Roche, Takeda; Speaker bureau/Expert testimony: Lilly, MSD,
Takeda; Research grant/Funding (institution): AstraZeneca, BMS, Celgene, Roche;
Travel/Accommodation/Expenses: BMS, Boehringer, MSD, Novartis
Mark Wroblewski: Angestellt bei der Firma AstraZeneca
Frank Griesinger: Beratungs‐ bzw. Gutachtertätigkeit: Astra Zeneca, Boehringer
Ingelheim, Novartis, Pzer, Roche, Bms, Msd, Celgene, Lilly, Takeda, Siemens,
Abbvie, Bayer
Honorare: Astra Zeneca, Boehringer Ingelheim, Novartis, Pzer, Roche, BMS,
MSD, Celgene, Lilly, Takeda, Siemens, Abbvie, Bayer, Finanzierung wissenscha-
licher Untersuchungen: Astra Zeneca, Boehringer Ingelheim, Novartis, Pzer,
Roche, BMS, MSD, Celgene, Lilly, Takeda, Siemens
520
First-Line Immunotherapy in Elderly Patients with Stage
iv Non-Small Cell Lung Cancer: an Early Ecacy and Safety
Assessment
Jonas Kuon 1, 2; Miriam Blasi 1; Heidrun Grosch 1; Petros Christopoulos 1, 2;
Christiane Wiedemann 1; Felix Herth 2, 3; Claus-Peter Heussel 2, 4, 5;
Albrecht Stenzinger 2, 6; Michael Thomas 1, 2
1Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg,
Deutschland
2Translational Lung Research Center Heidelberg (TLRC-H), Member of the
German Center for Lung Research (DZL), Heidelberg, Deutschland
3Pneumology, Thoraxklinik at Heidelberg University Hospital, Heidelberg,
Deutschland
4Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik
at Heidelberg University Hospital, Heidelberg, Deutschland
5Diagnostic and Interventional Radiology, University Hospital Heidelberg,
Heidelberg, Deutschland
6Institute of Pathology, University Hospital, Heidelberg, Heidelberg,
Deutschland
Purpose: Clinical trials have shown benets on both PFS and OS of add-
ing pembrolizumab to standard chemotherapy (CT) in patients with pre-
vious untreated stage IV NSCLC without EGFR or ALK mutations, lead-
ing to approval of rst-line immunotherapy (IO) regardless of the PDL-1
status. Elderly patients are still underrepresented in main clinical trials,
thus there is an unmet need of evaluating safety, ecacy and predictors for
toxicity of novel therapies in this challenging population.
Methods: We retrospectively evaluated clinical features, response rate
(RR) and toxicities of 58 patients aged ≥70 years diagnosed with stage IV
NSCLC treated in our clinic with rst-line IO, both as monotherapy and
in combination with CT, from January 2017.
Results: e mean age was 75.8 years. 17 patients (29%) were treat-
ed with IO plus CT. Among all patients the RR was 59% and the mean
time to response was 6.3 weeks with no signicant dierences between
the two treatment groups (p=0.32 and p=0.07, respectively). 27 patients
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(47%) experienced immune-related adverse events (irAE), 22% of which
reached grade 3, with no signicant dierences comparing the two groups
(p=0.6). e most frequent early-detected irAEs involved thyroid (17% of
patients), lungs (10%) and liver (9%). Neutropenia of grade ≥ 3 occurred
in 4 patients treated with the combination therapy. Treatment was dis-
continued due to toxicity in 7 cases (14%) and 8 patients needed a che-
motherapy dose reduction. Both Charlson Comorbidity Index (CCI) and
age-adjusted CCI were identied as signicant predictors for toxicity of
any type (p=0,026 and p=0,008, respectively).
Conclusions: In this early assessment no signicant dierences regarding
ecacy or toxicity in patients ≥ 70 years old with stage IV NSCLC treated
with either rst-line IO alone or in combination with CT were revealed.
Notably, these preliminary data show a higher irAE rate than expected
based on previous publications. e presence of comorbidities can predict
the toxicity occurrence. We will extend this study to gain deeper insight
into these issues.
544
Mortality After Radiotherapy or Surgery in The Treatment of
Early Stage Non-Small-Cell Lung Cancer: a Population Based
Study on Recent Developments
Christian Ostheimer; Christoph Evers; Franziska Palm; Dirk Vordermark;
Rafael Mikolajczyk; Daniel Medenwald
Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland
Purpose: Stereotactic body radiotherapy (SBRT) can achieve high tumour
control with limited toxicity for inoperable early stage non-small-cell lung
cancer (NSCLC) patients. is study aims to assess alterations in the sur-
vival of early stage lung cancer in relation to therapy across recent years.
Methods: e German Epidemiologic Cancer Registries were assessed.
Periods according to availability of SBRT: (1) 2000-2003 (pre-SBRT), (2)
2004-2007 (interim) and (3) 2007-2014 (broad availability of SBRT). To
assess the association of cancer related parameters with mortality, hazard
ratios (HR) from Cox proportional hazards models were computed. To
evaluate the change of treatment related mortality, we performed interac-
tion analyses and the relative excess risk due to interaction (RERI, additive
scale) was computed.
Results: 16,292 patients with UICC stage I NSCLC diagnosed between
2000 and 2014 were analysed. Radiotherapy utilization increased from 5%
in pre-SBRT era to 8.8% aer 2007. In univariate analyses survival in the
whole cohort improved only marginally when 2000-2003 is compared to
2004-2007 (HR=0.92, 95% CI: 0.85-1.01) or 2008-2014 (HR=0.93, 95% CI:
0.86-1.01). Comparing surgery and radiotherapy the interaction analysis
revealed a stronger improvement for radiotherapy (multiplicative scale for
2000-2003 vs. >2007: 0.78, 95% CI: 0.62-0.98), while risk of death was
lower in the surgery group irrespective of period. On an additive scale,
treatment*period interaction revealed a RERI for 2000-2003 vs. >2007 of
-1.18 (95% CI: -1.84, -0.52).
Conclusions: Using population-based data, we observed a survival im-
provement in stage I lung cancer over time. With an increasing utilization
of radiotherapy, a stronger improvement occurred in patients treated with
radiotherapy when compared to surgery.
Reference:
1. Palma D, et al. Impact of Introducing Stereotactic Lung Radiotherapy for El-
derly Patients With Stage I Non–Small-Cell Lung Cancer: A Population-Based
Time-Trend Analysis. J Clin Oncol 2010;35: 5153-5159.
Disclosure Statement: no conict of interest
555
Deciphering The Tumor Immune Microenvironment Based on
CD8+ TiL Density and PD-L1 Expression in Locally Advanced
NSCLC Treated with Concurrent Chemoradiotherapy
Lukas Käsmann 1; Kathrin Gennen 1; Julian Taugner 1; Chukwuka Eze 1;
Olarn Roengvoraphoj 1; Jens Neumann 2; Amanda Tufman 3; Michael
Orth 1; Simone Reu 4; Claus Belka 1; Farkhad Manapov 1
1University Hospital, LMU Munich, Department of Radiation Oncology, Munich,
Deutschland
2University Hospital, LMU Munich, Department of Pathology, Munich,
Deutschland
3University Hospital, LMU Munich, Division of Respiratory Medicine and
Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology
Centre Munich, Munich, Deutschland
4University Hospital Wuerzburg, Department of Pathology, Würzburg ,
Deutschland
Purpose: e prognostic value of the tumor immunity microenviron-
ment (TIME) in multimodal treatment for locally advanced non-small
cell lung cancer (LA-NSCLC) is controversal. e aim of this study was
to investigate the prognostic value of PD-L1 expression on tumor cells
in combination with CD8+ tumor stroma-inltrating lymphocytes (TILs)
density in inoperable LA-NSCLC treated with concurrent chemoradio-
therapy (CRT).
Methods: Data of 31 inoperable LA-NSCLC patients treated with concur-
rent CRT with tumor biopsy samples at initial diagnosis were evaluated.
PD-L1 expression on tumor cells (0% versus ≥1%), CD8+ TILs density
(0-40% vs. 41-100%) and TIME according to classication of Zhang et al.
[1] were evaluated for potential prognostic value in terms of local control,
progressions-free (PFS) and overall survival (OS) as well as correlations
with clinicopathological features investigated.
Results: Median OS was 14months (range: 3-167 months). e OS rates
at 1- and 2 years were 68% and 20%. Local control of the entire cohort
at 1 and 2 years were 74% and 61%, respectively. Median and PFS at 1
and 2 years were 13±1,4 months, 58% and 19%. PD-L1 expression <1%
on tumor cells was associated with improved OS, PFS and local control
in patients treated with concurrent CRT. Evaluation of TIME appears to
be an independent prognostic factor for local control, PFS and OS. e
longest and shortest OS were achieved in patients with typ I (PD-L1neg/
CD8low) and type IV (PD-L1pos/CD8low) tumors (median OS: 57±37
vs. 10±5months, p=0.05), respectively.
Conclusions: Assessment of the tumor immunity microenvironment
(TIME) by PD-L1 expression on tumor cells and CD8+ TILs density is a
predictive biomarker in patients treated with concurrent CRT for inoper-
able LA-NSCLC.
Reference:
1. Zhang Y, Chen L (2016) Classication of advanced human cancers based on
tumor immunity in the MicroEnvironment (TIME) for cancer immunothera-
py. JAMA Oncol 2:1403–1404
Disclosure Statement: Nothing to declare
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579
First Subsequent Treatment After Discontinuation
of Durvalumab in Unresectable, Stage III NSCLC Patients
from PACIFIC
Martin Faehling 1; David Planchard 2; Byoung Chul Cho 3;
Jhanelle Elaine Gray 4; Luis G. Paz-Ares 5; Mustafa Ozguroglu 6;
Augusto E. Villegas 7; Davey B. Daniel 8; David Vicente 9; Shuji Murakami 10;
Rina Hui 11; Takayasu Kurata 12; Alberto Chiappori 13; Ki Hyeong Lee 14;
Yu Gu 15; Catherine Wadsworth 16; Phillip A. Dennis 17;
Scott Joseph Antonia 13; Maike de Wit 18
1Klinikum Esslingen, Esslingen, Deutschland
2Gustave Roussy, Villejuif, Frankreich
3Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Südkorea
4Lee Mott Cancer Center and Research Institute, Tampa, United States
55Hospital Universitario 12 de Octubre, CiberOnc, Universidad Complutense
and CNIO, Madrid, Spanien
6Istanbul University-Cerrahpaşa,, Cerrahpaşa School of Medicine, Istanbul,
Turkey
7Cancer Specialists of North Florida, Jacksonville, United States
8Tennessee Oncology, Chattanooga, United States
9Hospital Universitario Virgen Macarena, Sevilla
10Kanagawa Cancer Center, Yokohama, Japan
11Westmead Hospital and the University of Sydney, Sydney, Australien
12Department of Thoracic Oncology, Kansai Medical University Hospital,
Hirakata, Japan
13H. Lee Mott Cancer Center and Research Institute, Tampa, United States
14Chungbuk National University Hospital, Chungbuk National University
College of Medicine, Cheongju, Südkorea
15Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan
16AstraZeneca, Aldeley Park, United Kingdom
17AstraZeneca, Gaithersburg, United States
18Vivantes Klinikum Neukoelln, Berlin, Deutschland
Purpose: In the phase 3 PACIFIC trial of unresectable, stage III NSCLC
patients (pts) without progression aer concurrent chemoradiotherapy
(cCRT), durvalumab (durva) signicantly improved PFS and OS with
similar safety compared to placebo (pbo). We performed exploratory
analyses to characterize 1st subsequent treatment (Tx) aer discontinu-
ation of durva.
Methods: Pts with WHO PS 0/1 and any tumor PD-L1 status were ran-
domized (2:1) 1–42 days aer ≥2 cycles of platinum-based cCRT to durva
10 mg/kg IV or pbo Q2W up to 12 months. Pts were classied by the use
or not of 1st subsequent Tx and category of 1st systemic Tx.
Results: As of Mar 22, 2018, 216/476 (45.4%) and 153/237 (64.6%) in
the durva and pbo arms, respectively, had a RECIST-based PFS event per
BICR (5.7% and 8.4% due to death). 195 (41.0%) and 128 (54.0%) received
1st subsequent Tx, most of which were systemic Tx (158 [33.2%] and 109
[46.0%]): PDCT (16.4% and 19.0%), SCT (8.6% and 8.4%), IT (4.2% and
13.5%) or TT (3.8% and 5.1%); 7.8% and 8.0% received RT only. Time to
1st subsequent therapy or death (TFST) was longer with durva vs pbo (HR
0.58; 95% CI 0.47–0.72; median 21.0 vs 10.4 months). Baseline character-
istics of pts with or without 1st subsequent Tx were similar, and similar
across durva or pbo arms. Best overall response to 1st systemic Tx will be
presented.
Conclusions: Due to longer PFS and fewer progression events with durva
vs pbo, fewer pts on durva required subsequent Tx and, per TFST, much
later. Baseline characteristics were similar for pts with or without 1st sub-
sequent Tx and pts who received 1st systemic Tx, except for pts who re-
ceived TT, as expected due to their molecular prole.
Disclosure Statement: funding by AstraZeneca
581
PD-L1 Expression in Primary Tumour vs Metastatic Samples in
The Phase 3 MYSTiC Study in First-Line Metastatic (m) NSCLC
T. Wehler 1; N. Reinmuth 2; A.-M. Boothman 3; B.C. Cho 4; K.H. Lee 5; A. Luft 6;
M.-J. Ahn 7; M. Scott8; J. Whiteley 8; J. Walker 9; V. Karwe 10;
P. Mukhopadhyay 11; P. Thiyagarajah 11; U. Scheuring 11; N. Rizvi 12;
M. de Wit 13
1Evangelisches Krankenhaus Hamm, Hamm, Deutschland
2Thoracic Oncology Department, Asklepios Lung Clinic, Munich-Gauting,
Deutschland
3Oncology Companion Diagnostics Unit, IMED Biotech Unit, AstraZeneca,
Cambridge, United Kingdom
4Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College
of Medicine, Seoul, Korea
5Medical Oncology, Chungbuk National University Hospital, Cheongju, Korea
6Oncology Department, Leningrad Regional Clinical Hospital, Lunacharskogo
Prospect, Russland
7Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University,
Seoul, Korea
8Diagnostic Development Unit, Precision Medicine, R&D Oncology, AstraZeneca,
Cambridge, United Kingdom
9Oncology Companion Diagnostics Unit, Precision Medicine and Genomics,
IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom
10Biostatistics, AstraZeneca, Gaithersburg, United States
11Global Medicines Development, AstraZeneca, Cambridge, United Kingdom
12Medical Oncology, Columbia University Medical Center, New York, New York,
United States
13Vivantes Netzwerk für Gesundheit GmbH, Berlin, Berlin, Deutschland
Purpose: PD-L1 expression determined by immunohistochemistry (IHC)
can be a useful biomarker to assess the likelihood of benet with an-
ti-PD-1/PD-L1 therapies in pts with mNSCLC. MYSTIC (NCT02453282)
was an open-label, Phase 3 study of durvalumab (D) ± tremelimumab vs
chemotherapy (CT) as rst-line treatment for mNSCLC; stratication
factors for randomisation included tumour cell (TC) PD-L1 expression
(≥25% vs <25%). While not statistically signicant, D showed a clinically
meaningful improvement in OS compared with CT (HR 0.76 [97.54% CI
0.56–1.02], p=0.036) in pts with PD-L1 TC ≥25%. We investigated wheth-
er the use of a primary tumour or metastatic site biopsy to determine PD-
L1 status impacted prevalence of TC ≥25% or clinical benet.
Methods: All pts enrolled in MYSTIC were assessed centrally for TC
staining for PD-L1 from tissue samples acquired <3 months (mo.) prior to
randomisation from either the site of the primary tumour or a distant me-
tastasis. Testing was performed using the VENTANA PD-L1 (SP263) IHC
assay. A post-hoc analysis evaluated prevalence, OS, ORR and duration of
response (DoR) in pts with PD-L1 TC ≥25% as determined using either a
primary tumour or a distant metastatic sample.
Results: Of 1118 pts randomised, 716 (64.0%) provided a primary tumour
sample and 402 (36.0%) provided a metastatic sample. e prevalence of
PD-L1 TC ≥25% assessed using primary vs metastatic samples was 43.0%
vs 44.8% (p=0.569). According to primary or metastatic site, median OS
for D vs CT was 15.8 vs 13.0 mo. (HR 0.81 [95% CI 0.59-1.11]) and 20.5 vs
12.6 mo. (HR 0.65 [95% CI 0.41-1.01]), respectively.
Conclusions: In MYSTIC, PD-L1 TC ≥25% prevalence was similar using
primary or metastatic samples. Favourable HRs for OS with D vs CT were
seen in pts with TC ≥25% expression as determined in either the primary
tumour or a metastatic site. Results should be interpreted with caution
given the retrospective nature of the analysis.
Reference:
1. NCT02453282 (release date: 25 May 2015)
Disclosure Statement: Funded by AstraZeneca
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591
Nationwide Tumor-Biological Testing Survey in Patients
with NSCLC in Germany – Current Results and Development
of Testing Behavior Since 2012
Helmut Ostermann 1; Dieter Ukena 2; Alexander Freitag 3
1University of Munich, Department of Hematology and Oncology, München,
Deutschland
2Bremen East Hospital, Department of Pneumology and Respiratory Medicine,
Bremen, Deutschland
3AstraZeneca, Oncology, Wedel, Deutschland
Purpose: Tumor-biological testing of patients with stage IV non-small-
cell lung cancer (NSCLC) is clinically indicated and endorsed by guide-
lines (with only few exceptions) because it enables the use of companion
diagnostic guided drug therapy from which many patients benet consid-
erably. Molecular testing for the biomarkers EGFR, ALK, ROS and BRAF
and immunohistochemical testing for PD-L1 should therefore be manda-
tory. We want to determine whether testing in Germany is performed as
per guideline recommendation.
Methods: Experienced oncologists in dierent types of health care insti-
tutions (certied lung cancer centers, university and non-university hos-
pitals and oce-based physicians) are asked to answer a questionnaire on
the details of testing. Data are analyzed by explorative analysis. e cur-
rent results are broken down by institution and compared with those from
previous years to analyze the development of test behavior.
Results: Previous surveys by us (in 2012 and in 2016) have shown that
EGFR mutation analysis was employed in clinical routine in 2012 and
increased signicantly by the end of 2016, when the last survey was con-
ducted. However, there is still potential for improvement in Germany in
terms of the optimal use of therapy options. In the last survey the number
of patients tested was 75% for EGFR, 66% for EML4-ALK, 41% for ROS1,
and 14% for BRAF. ese data will again be examined in the new survey
which is currently ongoing. We will present the results and discuss the
development of testing in Germany from 2012 to 2019.
Conclusions: Despite guideline recommendations it appears that there is
still a signicant number of patients in whom tumor-biological testing is
not done and, therefore, access to optimal treatment may not be possible.
e results that will be presented will clarify whether important improve-
ments in the rate of testing have occurred.
Disclosure Statement: is study was supported by Astra Zeneca
Dieter Ukena received honoraria for speaker activities from Amgen, AstraZeneca,
Boehringer Ingelheim, Bristol Myers Squibb, MSD, Roche. He received honoraria
for consulting activities from AstraZeneca, Boehringer Ingelheim, MSD, Takeda.
Alexander Freitag is an employee of AstraZeneca.
594
Evaluation of Combined Biomarkers for Tumor Response to
Immunotherapy (I/O) in Patients with Advanced Non-Small
Cell Lung Cancer (NSCLC)
Hayat Ramdani 1; Markus Falk 2; Stefanie Schatz 2; Lukas C. Heukamp 2;
Markus Tiemann 2; Ed Schuuring 3; Harry Groen 3; Frank Griesinger 1
1Universitätsklinik für Innere-Medizin und Onkologie, Pius Hospital Oldenburg ,
Oldenburg, Deutschland
2Institur für Hämatopathologie Hamburg, Lung cancer network NOWEL ,
Hamburg, Deutschland
3Universiteit Groningen, Dept. Pathology, University of Groningen, Groningen,
Niederlande
Purpose: Immune checkpoint inhibitors have revolutionized NSCLC
treatment. At present, the only established predictive biomarker for I/O
therapy stratication are PD-L1 expression and MSI status. However, the
expression of PD-L1 is limited by heterogeneous expression and even high
expressors not always respond to I/O therapy. e aim of the study is to
evaluate the value of combinations of positive (Tumor Mutational Bur-
den, PD-L1) and negative (a.o. CD73 expression and inactivating STK11
mutations) predictive markers in patients (pts) with advanced NSCLC on
I/O therapy.
Methods: A retrospective study was performed on a cohort of 54 pts with
advanced NSCLC that have been treated with I/O between 2015/2018.
Pts were selected by the availability of tumor tissue and based on tumor
response evaluated by RECIST v1.1 criteria: only patients with durable
tumor response (CR,PR > 6 months) and patients with no tumor response
(PD as best response) were analyzed for biomarkers: hybrid capture NGS
assay for TMB (New Oncology) including STK11 mutations and IHC
tests for PD-L1, CD73 and VISTA. Adjusted Cox regression and ROC
analysis will be performed to evaluate the predictive value of the dierent
biomarkers.
Results: 43/54 pts received nivolumab, 11/54 pembrolizumab in dierent
therapy lines (1st to 5th). 24 pts were dened as having a durable tumor
response (median PFS 44 months, median OS 53 months; p<0.0001) 30
pts as primary progressors (median PFS 2 months, median OS 12 months;
p<0.0001). In 30/54 pts enough material was available for TMB testing. In
13 durable responders median TMB-value was 13.28 mt/Mb versus 11.00
mt/Mb in 17 primary non-responders. STK11 mutations were observed in
3/17 primary non-responders (10%) vs. 0/13 in durable responders (0%).
Additional analyses of the biomarkers will be presented at the meeting
with correlative data of the parameters analyzed.
Conclusions: Our results suggest that integrating several biomarkers in-
cluding positive and negative predictive markers may correlate better with
responses to I/O than PD-L1 and TMB alone.
Disclosure Statement: no COI
604
Screening of Pleural Mesothelioma Cell Lines for Kinase
Activity May Identify New Targets to Overcome of Therapy
Resistance in Patients Receiving Platin-Based Chemotherapy
Sabrina Borchert 1; Pia Maria Suckrau 1; Michael Wessolly 1;
Elena Mairinger 1; Balazs Hegedus 2; Thomas Hager 1; Thomas Herold 1;
Wilfried Eberhardt 3; Jeremias Wohlschläger 1, 4; Clemens Aigner 2;
Agnes Bankfalvi 1; Kurt Werner Schmid 1; Robert Walter 1, 5;
Fabian Dominik Mairinger 1
1Institute of Pathology, University Hospital Essen, University of Duisburg-Essen,
Essen, Deutschland
2Department of Thoracic Surgery and Thoracical Endoscopy, Ruhrlandklinik,
West German Lung Centre, University Hospital Essen, University of Duisburg-
Essen, Essen, Deutschland
3Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, University of Duisburg-Essen, Essen, Deutschland
4Department of Pathology, Diakonissenkrankenhaus Flensburg, Flensburg,
Deutschland
5Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University
of Duisburg-Essen, Essen, Deutschland
Purpose: Malignant pleural mesothelioma (MPM) is a rare, predomi-
nantly asbestos-related and biologically highly aggressive tumor leading
to a dismal prognosis. Platin-compounds are standard chemotherapeutic
agents and still a hallmark of chemotherapy for MPM. e reasons for
the rather poor ecacy largely unknown. Kinase activity might inuence
cellular response to these regimes.
Methods: We screened dierent MPM cell lines for overall phosphoryla-
tion signatures as well as kinase activity with respect to cellular response
to cisplatin-based therapeutics in a high-throughput manner using the
highly innovative technique PamGene. Cell state analysis including apop-
tosis, necrosis as well as cell viability was performed by using enzyme-ac-
tivity and uorescent-based assays.
Results: Cisplatin alters phosphorylation aecting cell cycle, migration,
adhesion, signal transduction, immune modulation and apoptosis of cells.
High phosphorylation, especially of ESR1, LAT, PTPN12 and PTPN6
aecting proliferation and the RAS-MAPK-Pathway, leads to platin re-
sistance. In cisplatin-responsive cell lines, phosphorylation of AKT1 and
GSK3B was reduced. Cisplatin-responsive cell lines showed elevated
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phosphorylation levels of JNK1/2/3, but decreased phosphorylation in
cisplatin-resistant NCI-H2452 cells.
Conclusions: Kinase phosphorylation and activity might play a crucial
role in cellular response to cytostatic agents. Cisplatin inuences phos-
phorylation patterns in tested cell lines with distinct features in cispla-
tin-resistant cell lines. Based on our results, the induction of p38 or
JNK1/3, or inhibition of AKT1 by e.g. BIA-6, might have synergistic eect
with platin-based strategies and therefore be a therapeutic approach to in-
duce apoptotic response to cisplatin treatment, thus potentially enhancing
patients’ outcome.
Disclosure Statement: e authors have no conicts of interest to disclose.
606
Impact of Metallothionein-Knockdown on Cisplatin Resistance
in Malignant Pleural Mesothelioma
Sabrina Borchert 1, 2; Pia Maria Suckrau 1; Robert Walter 1, 2, 3;
Michael Wessolly 1, 2; Elena Mairinger 1, 2; Julia Radke 1, 2; Balazs Hegedüs 4;
Thomas Hager 1, 2; Thomas Herold 1, 2; Wilfried Eberhardt 3, 5;
Jeremias Wohlschläger 1, 6; Clemens Aigner 4; Agnes Bankfalvi 1, 2;
Kurt Werner Schmid 1, 2; Fabian Dominik Mairinger 1, 2
1Institute of Pathology, University Hospital Essen, University of Duisburg-Essen,
Essen, Deutschland
2German Cancer Consortium (DKTK), Partner Site University Hospital Essen,
Universitätsklinikum Essen, Essen, Deutschland
3Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University
of Duisburg-Essen, Essen, Deutschland
4Department of Thoracic Surgery and Thoracic Endoscopy, Ruhrlandklinik,
University Hospital Essen, University of Duisburg-Essen, Essen, Deutschland
5Department of Medical Oncology, West German Cancer Centre, University
Hospital Essen, University of Duisburg-Essen, Essen, Deutschland
6Department of Pathology, Diakonissenkrankenhaus Flensburg, Flensburg,
Deutschland
Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor
with dismal prognosis. Platinum-based chemotherapy is standardly
used for treatment. e expression of metallothioneins (MT) has been
identied as a reason for cisplatin resistance in MPM. We hypothesized
that knockdown of MT expression might improve response to cisplatin
treatment.
Methods: MT expression of three MPM cell lines and the lung broblast
cell line MRC 5, and their sensitivity to cisplatin treatment have been eval-
uated. Knockdown of MT1A, 1B and 2A expression was induced by RNA
interference and subsequently, MT expression was measured using qPCR.
Cell viability, necrosis and apoptosis before and aer incubation with cis-
platin was analyzed.
Results: MT2A gene expression was observed in all MPM cell lines, with
highest expression in NCI H2452 and NCI H2052. Gene expression levels
of MT1A and MT1B were very low or absent. e immunohistochemical
protein expression of MT-I/II correspond to MT2A gene expression lev-
els. Especially for MSTO 211H, a strong induction of MT2A expression
was observed during cisplatin treatment, indicating a platin-dependent
adaption mechanism. Additionally, a MT2A dependent response to cis-
platin treatment was observed, leading to three dierent MT based phe-
notypes. Knockdown of MT2A signicantly induced apoptosis during
cisplatin treatment with strongest induction of apoptosis in each of the
MPM cell lines, but in dierent phenotypes. We observed a therapeutic
meaningful eect of MT2A knockdown and subsequent cisplatin treat-
ment in MSTO 211H cells.
Conclusions: MT2A seems to be part of the underlying mechanism of
cisplatin resistance in MPM. Especially in MSTO 211H cells, major eects
by knockdown of MT2A expression could be observed, verifying our hy-
pothesis of an MT driven resistance mechanism in MPM. Inhibition of
MT2A could be used as a powerful tool to boost response rates to cispla-
tin-based therapy in vitro. ese data carry the potential to boost clinical
outcome and management of MPM in the future.
Disclosure Statement: e authors have nothing to disclose.
607
Early Clearance of Plasma EGFR Mutations As a Predictor
of Response to Osimertinib and Comparator EGFR-TKiS
in the Flaura Trial
Helge Bischo 1; Caicun Zhou 2; Fumio Imamura 3; Ying Cheng 4;
Isamu Okamoto 5; Byoung Chul Cho 6; Meng Chih Lin 7; Margarita Majem 8;
Oliver Gautschi 9; Jhanelle Elaine Gray 10; Michael J. Boyer 11;
Juliann Chmielecki 12; Ryan Hartmaier 13; Krishna Bulusu 13; J Carl Barrett 13;
Rachel Hodge 13; Matilde Saggese 13; Astrid Mckeown 13;
Suresh S. Ramalingam 14; Niels Reinmuth 15
1Thoraxklinik Heidelberg gGmbH, Heidelberg, Deutschland
2Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
3Department of Thoracic Oncology, Osaka International Cancer Institute,
Osaka, Japan
4Department of Oncology, Jilin Province Cancer Hospital, Changchun, China
5Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan
6Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College
of Medicine, Seoul, Südkorea
7Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung
Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan
8Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau,
Barcelona, Spanien
9University of Berne and Cantonal Hospital of Lucerne, Lucerne, Schweiz
10Department of Thoracic Oncology, Mott Cancer Center and Research
Institute, Tampa, United States
11Department of Medical Oncology, Chris O’Brien Lifehouse, Camperdown,
Australien
12Translational Sciences, IMED Biotech Unit, AstraZeneca, Waltham,
United States
13AstraZeneca, Cambridge, United Kingdom
14Winship Cancer Institute, Emory University, Atlanta, United States
15Asklepios Fachkliniken München‐Gauting , Gauting, Deutschland
Purpose: In the FLAURA trial, osimertinib showed superior ecacy to
comparator EGFR-TKIs as rst line treatment for EGFR mutation-posi-
tive (EGFRm) advanced NSCLC. In an exploratory analysis, we investi-
gated clinical outcomes associated with detection of plasma EGFRm at 3
or 6 weeks (wks) aer start of treatment.
Methods: Treatment-naive patients (pts) with EGFRm locally advanced
or metastatic NSCLC were randomized 1:1 to receive osimertinib 80 mg
or comparator EGFR-TKIs (getinib 250 mg QD or erlotinib 150 mg QD).
Plasma EGFR mutation analysis was conducted at baseline (BL), wks 3
and 6 by droplet digital PCR. Clearance was dened as undetectable levels
of EGFRm in ctDNA at wks 3/6, where they were detectable at BL. PFS
was investigated based on early clearance of EGFRm.
Results: In total 489/556 (88%) pts (osimertinib: 244/279; comparator:
245/277) had evaluable ctDNA at BL and wks 3/6. Of these, 342/489 (70%;
osimertinib: 168/244; comparator: 174/245) had detectable BL EGFRm
and were included in this analysis. See table.
Conclusions: Clearance of plasma EGFRm aer 3/6 wks of EGFR-TKI
therapy was associated with a numerical improvement in PFS. e e-
cacy of osimertinib was superior to comparator EGFR-TKIs regardless of
clearance status
References:
Disclosure Statement: funding AstraZeneca
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630
Integrated Biobanking and Tumor Model Establishment
from Lung Cancer Patients Provides Excellent Tools
for Modern Precision Medicine
Christina Mullins 1; Njanja Enz 1; Jana Rol 2; Michael Becker 2;
Michael Linnebacher 3; Wolfgang Jungraithmayr 1
1Thoraxchirurgie, Universitätsmedizin Rostock, Rostock, Deutschland
2epo - experimental pharmacology & oncology berlin-buch GmbH, Berlin,
Deutschland
3Chirurgie, Universitätsmedizin Rostock, Rostock, Deutschland
Purpose: e rst tumor cell line was established in the 1950s, in vivo
models followed suit in the 1960s. e current focus is on patient-derived
models; especially the patient derived xenogras (PDX) are very popular
for preclinical drug development to mimicking clinical trials. In paral-
lel, the generation of large biobanks, enabling individualized therapy ap-
proaches, at least on a patho-molecular level of the tumor, has become
standard in comprehensive cancer centers.
Methods: Patients operated on at the University Medical Center Rostock
from 2010 onward participated in the HROLu collection (HRO: Hanses-
tadt Rostock; Lu: lung cancer). Samples were collected using strict SOP in-
cluding blood, tumor tissue as well as adjacent normal epithelium. Patient
and tumor data including classication, sub-type, and results of model
establishment are the essential pillars.
Results: In total, 39 patients with either a primary lung tumor (n=27) or
a metastasis (n=12) of a primary brain tumor were included so far. e
male-to-female ratio was 1.6: 24 male and 15 female patients. e mean
age at time of surgery was 61 years, ranging from 36 to 80 years. e sub-
type distribution in the primaries was: one small cell carcinoma and 20
adenocarcinomas, 1 squamous cell carcinomas, 1 large cell carcinoma
and 1 adenosquamous and in the metastases: 5 adenocarcinomas, 3 squa-
mous cell carcinomas, 1 large cell carcinoma and 3 not further dened
metastases. Patient-derived tumor model establishment attempts in vitro
were successful for 3/33 (9%); however 12 are still ongoing. A PDX could
be established in 3/5 (60%). Sensitivity of the PDX towards a variety of
therapeutics commonly used in tumor therapy was tested. One PDX was
highly sensitive towards most of the therapeutics tested; one PDX was
highly sensitive towards Gemcitabine and Bevacizumab, the third PDX
was highly sensitive towards Paclitaxel.
Conclusions: ese patient individual tumor models and biobanked ma-
terials represent a valuable basis for translational and preclinical studies.
Disclosure Statement: none to declare
635
Predicting Response and Outcome After Platin-Based
Chemotherapy and New, Targeted Approaches in Malignant
Pleural Mesothelioma
Fabian Dominik Mairinger 1; Sabrina Borchert 1; Michael Wessolly 1;
Elena Mairinger 1; Jens Kollmeier 2; Daniel Christoph 3, 4; Wilfried Eberhardt 3;
Balazs Hegedus 5; Pia Maria Suckrau 1; Thomas Hager 1;
Saskia Roxanne Sydow 6; Henning Ohlig 1; Martine Wyrich 1; Julia Radke 1;
Thomas Herold 1; Thomas Mairinger 7; Clemens Aigner 5;
Kurt Werner Schmid 1; Agnes Bankfalvi 1; Jeremias Wohlschläger 1, 8;
Robert Walter 1, 9
1Institute of Pathology, University Hospital Essen, University of Duisburg-Essen,
Essen, Deutschland
2Institute of Pneumology, Helios Klinikum Emil von Behring, Berlin, Deutschland
3Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, University of Duisburg-Essen, Essen, Deutschland
4Department of Internistic Oncology, Kliniken Essen Mitte, Essen, Deutschland
5Department of Thoracic Surgery and Thoracical Endoscopy, Ruhrlandklinik,
University Hospital Essen, University of Duisburg-Essen, Essen, Deutschland
6Institute of Pathology, Charité Universitaetsmedizin, Berlin, Berlin, Deutschland
7Department of Tissue Diagnostics, Helios Klinikum Emil von Behring, Berlin,
Deutschland
8Department of Pathology, Diakonissenkrankenhaus Flensburg, Flensburg,
Deutschland
9Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University
of Duisburg-Essen, Essen, Deutschland
Purpose: Platin-analoga are the drug of choice for the treatment of
malignant pleural mesothelioma (MPM), resulting in response rates of
merely 6 to 16%. e reasons for the rather poor ecacy largely unknown.
Against the unsatisfactory background, we investigated the impact of
platinum uptake, -metabolism as well as DNA-damage response on
therapy outcome.
Methods: FFPE samples of 236 MPM patients and healthy tissue from
20 patients with spontaneous pneumothorax were used. For function-
al validation, 6 cell lines were analyzed in the same manner. Specimens
were screened by digital gene expression analysis for 366 mRNAs and
800 important miRNAs using NanoString technology. Additionally, 48
selected candidate genes were analyzed in a multiplex manner using the
PlexSet chemistry. Complementary, we discovered gene expression lev-
els of signicant targets via qPCR and protein expression levels via IHC.
Methylation patterns were analyzed of 284 dierent CpG sites via mass
spectrometry (MassARRAY EpiTYPER). To proof casuistic association,
viability, necrosis and apoptosis of all cell lines were analyzed before and
aer incubation with cisplatin. Knock-down of target genes was induced
by RNA interference.
Results: mRNA levels of DDR pathway members (MMR, BER, NER) are
signicantly associated with response to chemotherapy as well as OS and
PFS in MPM patients. Especially genes involved in TP53-mediated DNA
damage recognition, those compiled under the term “BRCAness” as well
as metallothioneins have been identied to mediate tumors’ response
rates against cisplatin-based chemotherapeutic regimes.
Conclusions: Beside modern therapeutic concepts, biomarker strati-
cation is urgently needed concerning nowadays state-of-the-art chemo-
therapeutic to improve and individualize MPM-therapy, saving non-re-
sponders from inecient and side-eect loaded therapy. Our results will
hopefully nd their way into clinical and pathological practice, resulting
in a benet for patients and improved clinical outcome.
Disclosure Statement: e authors have nothing to disclose.
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2018
Index
2018
638
Using German Claims Data to Characterize Real-World
Treatment Patterns in Cancer Patients – The Example of
Crizotinib
Sarina Schwarz 1; Katja Oppelt 1; Ulrike Haug 1, 2
1Leibniz-Institut für Präventionsforschung und Epidemiologie - BIPS, Bremen,
Deutschland
2Fachbereich 11 der Universität Bremen: Human- und
Gesundheitswissenschaften, Bremen, Deutschland
Purpose: To explore the potential of German claims data for characteriza-
tion of real-world treatment patterns in oncology, exemplied by patients
treated with crizotinib which is approved for a certain subtype of non-
small cell lung cancer (LC).
Methods: We used claims data from the German Pharmacoepidemiolog-
ical Research Database (short: GePaRD, information on ~25 million per-
sons), to identify patients with at least one crizotinib dispensation. Each
individual was followed as long as possible, longest 2004 until 2016. We
dened rst line therapy as the rst antineoplastic therapy (inpatient or
outpatient) and subsequent therapies as second or later line therapy. We
described patients regarding age, sex, codes for LC and metastases, num-
ber of crizotinib dispensations, as well as sequence of oncologic therapies
and death.
Results: In total, we identied 348 patients under crizotinib (56% female,
mean age: 58 years). 96% of the patients had a LC diagnosis code and 88%
had metastases coded within 6 months aer the rst LC diagnosis coded
in GePaRD. e mean time between rst LC diagnosis and rst crizotinib
dispensation was 16 months. On average, there were 8 crizotinib dispen-
sations per patient. 25% of patients received crizotinib as rst line therapy,
77% received a non-targeted chemotherapy during the study period and
14% received a non-targeted chemotherapy aer crizotinib discontinu-
ation. 11% of patients died while treated with crizotinib and 16% died
within 3 months aer discontinuing crizotinib therapy.
Conclusions: Using GePaRD we found treatment patterns regarding
crizotinib consistent with other studies and could provide detailed infor-
mation on its utilization. e results underline the potential of German
claims data for real-world monitoring of oncologic drug utilization.
Disclosure Statement: None.
644
Mutations in CTDNA Associated with Sensitivity or Resistance
to Immunotherapy in mNSCLC: Analysis from The Mystic Trial
T. Wehler 1; N. Rizvi 2; B.C. Cho 3; K.H. Lee 4; A. Luft 5; M.-J. Ahn 6; V.
Papadimitrakopoulou 7; J. Heymach 7; S. Peters 8; U. Scheuring 9; H. Si 10;
J. Ye 10; M. Kuziora 10; S. Wu 12; F. Liu 10; B. Higgs 10; N. Reinmuth 11
1Evangelisches Krankenhaus Hamm, Hamm
2Columbia University Medical Center, , New York, United States
3Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Südkorea
4Chungbuk National University Hospital, Chungbuk National University College
of Medicine, Cheongju, Südkorea
5Leningrad Regional Clinical Hospital, St. Petersburg, Russland
6Samsung Medical Center, Seoul, Südkorea
7The University of Texas MD Anderson Cancer Center, Houston, United States
8Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne,
Schweiz
9AstraZeneca, Cambridge, United Kingdom
10AstraZeneca , Gaithersburg, United States
11Asklepios Lung Clinic, München-Gauting, Gauting, Deutschland
Purpose: Tumour mutational burden (TMB) is associated with improved
overall survival (OS) to immunotherapy in patients with metastatic non-
small cell lung cancer (mNSCLC). Prior studies suggest that mutations
in STK11 (LKB1) are associated with resistance to PD-1/PD-L1 inhibitor
monotherapy but the associations between a broader panel of genomic
alterations and response to anti-PD-L1 monotherapy or anti-PD-L1/anti-
CTLA-4 combination therapy are not well characterised. MYSTIC was a
Phase 3 trial of rst-line durvalumab (anti-PD-L1) ± tremelimumab (anti-
CTLA-4) versus platinum-based doublet chemotherapy in patients with
mNSCLC without EGFR mutations or ALK rearrangements. In MYSTIC,
while not statistically signicant, a clinically meaningful improvement
in OS was observed with rst-line durvalumab versus chemotherapy in
patients with mNSCLC and PD-L1 expression in ≥25% of tumour cells
(TC ≥25%). Durvalumab + tremelimumab did not improve OS versus
chemotherapy in patients with PD-L1 TC ≥25%, but showed promising
OS and PFS in an exploratory analysis in patients with blood TMB
(bTMB) ≥20 mut/Mb. Associations between selected gene mutations and
outcomes are being explored in MYSTIC.
Methods: Circulating tumour DNA from baseline blood specimens was
proled using the GuardantOMNI platform. Samples were available from
1003 patients [89.7% of ITT]; of these 943 samples were sequenced. Sur-
vival outcomes and response rates will be analysed in patients with or
without nonsynonymous somatic mutations in KRAS, STK11 (LKB1),
KEAP1 or ARID1A and in association with bTMB status.
Results: Results will be presented on frequency of gene mutations in the
total population. OS and objective response rates will be reported based
on the presence of gene mutations for both the overall population and for
patients who had bTMB above and below designated thresholds.
Conclusions: Conclusions will be based on ndings.
Disclosure Statement: funding by AstraZeneca
652
Adriatic: a Phase III Trial of Durvalumab +/- Tremelimumab
After Concurrent Chemoradiation for Patients with Limited
Stage Small Cell Lung Cancer
F. Griesinger 1; S. Senan 2; N. Shire 3; G. Mak 3; W. Yao 3; H. Jiang3; M. Thomas 5
1Pius-Hospital Oldenburg, Oldenburg, Deutschland
2Department of Radiation Oncology, Vrije Universiteit Amsterdam, Cancer
Center Amsterdam, Amsterdam, Niederlande
3AstraZeneca, Gaithersburg, MD, Gaithersburg, United States
5Thoraxklinik am Universitätsklinikum Heidelberg, Universitätsklinikum
Heidelberg, Heidelberg, Deutschland
Purpose: Limited stage small-cell lung cancer (LS-SCLC), which represents
30% of newly diagnosed SCLC, remains an area of high unmet medical need.
Standard of care, which has not changed for several decades, consists of curative
intent platinum-based chemotherapy concurrent with radiotherapy (cCRT)
followed by prophylactic brain irradiation (PCI) and observation. Despite
good response to cCRT, outcomes remain poor, with median progression-free
survival (PFS) 15 months and overall survival (OS) 25 months. Durvalumab
(D) is a selective, high-anity, human IgG1 monoclonal antibody (mAb) that
blocks programmed cell death ligand-1 binding to programmed cell death-1
and CD80. Tremelimumab (T) is a selective human IgG2 mAb against CTLA-
4. D demonstrated a PFS and OS advantage over placebo in locally advanced
NSCLC following cCRT. D and D + T demonstrated a tolerable safety prole
and antitumour activity in pretreated extensive stage SCLC. e ADRIATIC
trial (NCT03703297) will assess if treatment with D + T is benecial vs placebo
in patients (pts) with LS-SCLC who have not progressed following cCRT.
Methods: ADRIATIC is a Phase 3, randomised, double-blind, multicentre,
placebo-controlled international trial. Pts (N600) will be randomised 1:1:1 to
receive D + placebo T, D + T, or dual placebo, stratied by Stage (I/II vs III)
and receipt of PCI at the investigator’s discretion (yes vs no). Eligible pts must
have conrmed inoperable Stage I–III LS-SCLC; WHO/ECOG PS 0/1; and
completed 4 cycles of cCRT with a response of stable disease or better within
1–42 days prior to randomisation. Pts will receive the assigned treatment until
clinical, RECIST v1.1-dened progressive disease, intolerable toxicity or for a
maximum of 24 months, whichever comes rst. Primary objectives are PFS
and OS for D + T vs placebo. Key secondary endpoints include health-related
quality of life, and safety and tolerability. Recruitment is ongoing.
Results:
Conclusions:
Reference:
1. Clinical trial identication: NCT0370329
Disclosure Statement: Funded by AstraZeneca
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2018
Index
2018
659
Frequency of Epidermal Growth Factor Receptor (EGFR)
Mutations in Stage IB–IIIA Egfr Mutation Positive Non-Small-
Cell Lung Cancer (NSCLC) After Complete Tumour Resection
M. Reck 1; M. Tsuboi 2; R.S. Herbst 3; T. John 4; M. Majem 5; J. Goldman 6;
S.-W. Kim 7; C.-J. Yu 8; J.E. Abrao Miziara 9; S. Novello 10; D. Urban 11;
C. Akewanlop 12; A. Öztürk 13; B.V. Quang 14; D. Kowalski 15; D. Marmol 16;
M. Marotti 16; G. Laus 16; Y.-L. Wu 17; W. Engel-Riedel 18
1Onkologischer Schwerpunkt, Airway Research Center North (ARCN), Deutsches
Zentrum für Lungenforschung, LungenClinic, Grosshansdorf , Grosshansdorf ,
Deutschland
2Department of Thoracic Surgery and Oncology, National Cancer Center
Hospital East, Kashiwa, Japan
3Medical Oncology, Yale School of Medicine and Yale Cancer Center, New
Haven, CT, United States
4Department of Medical Oncology, Austin Health, Melbourne, Australien
5Medical Oncology Services, Hospital de la Santa Creu i Sant Pau, Barcelona,
Spanien
6 University of California Los Angeles, Los Angeles, CA, United States
7Asan Medical Center, Seoul, South Korea
8Department of Internal Medicine, National Taiwan University Hospital and
National Taiwan University College of Medicine, Taipei, Taiwan
9Department of Thoracic Surgery, Barretos, Brasilien
10Oncology Department, University of Turin, AOU San Luigi, Turin, Italien
11Department of Medical Oncology, Institute of Oncology, Chaim Sheba
Medical Center, Tel Hashomer, aliated to Sackler Faculty of Medicine, Tel Aviv
University, Ramat Gan, Israel
12Division of Medical Oncology, Department of Internal Medicine, Faculty of
Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
13Department of Medical Oncology, Süreyyapaşa Chest Diseases and Thoracic
Surgery Training and Research Hospital, Istanbul, Turkey
14Hanoi Oncology Hospital, Hanoi, Viet Nam
15Department of Lung Cancer and Chest Tumours, Maria Sklodowska-Curie
Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
16AstraZeneca, Cambridge, United Kingdom
17Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital
and Guangdong Academy of Medical Sciences, Guangzhou, China
18Klinikum der Stadt Köln gGmbH, Köln, Deutschland
Purpose: Data on the frequency of EGFR mutations in patients (pts) with
NSCLC potentially eligible for adjuvant therapy are limited. Osimertinib,
a 3rd-generation, irreversible, oral EGFR-tyrosine kinase inhibitor (TKI),
potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and
EGFR T790M mutations and has shown ecacy in the CNS. e ADAURA
study (NCT02511106) will assess osimertinib as adjuvant therapy in ear-
ly-stage NSCLC aer complete resection. Here we report frequency of the
most common EGFR activating mutations from pts screened for ADAURA.
Methods: ADAURA is a Phase III, double-blind, randomised, place-
bo-controlled study assessing ecacy and safety of osimertinib vs placebo
in adult pts with mainly non-squamous histology, stage IB–IIIA EGFRm
NSCLC, following complete tumour resection, without or aer adjuvant
chemotherapy. At screening, EGFR mutations associated with EGFR-TKI
sensitivity (ex19del, L858R), alone or in combination with exon 20 inser-
tion, G719X, S768I, T790M or L861Q were centrally assessed from resect-
ed tumour samples using the cobas® EGFR Mutation Test (Roche).
Results: In total, 2447 pts were screened. Median age was 63 years (range
23–88), 54% were female, and 61% were non-Asian. At screening, 1087 (44%)
pts were EGFR mutation positive; 110/2447 (4%) pts had an unknown/une-
valuable test result. Of pts EGFR mutation positive, the most common muta-
tions were ex19del and L858R in 572 (53%) and 458 (42%) pts, respectively;
exon 20 insertion, G719X, T790M, S768I, and L861Q mutations occurred in
28 (3%), 24 (2%), 19 (2%), 11 (1%) and 8 (1%) pts, respectively. Mutations
occurred alone or in combination. A higher proportion of EGFR mutation
positive pts were Asian vs non-Asian (681 [63%] vs 402 [37%]; 4 pts missing)
and female vs male (755 [69%] vs 331 [30%]; 1 pt missing).
Conclusions: is analysis shows a high prevalence of EGFRm mutations
in Asian and female pts with stage IB–IIIA NSCLC following complete
resection, which is consistent with the advanced setting.
Reference:
1. NCT02511106
Disclosure Statement: Funded by AstraZeneca
693
Predictors and Eects of Reduced Chemotherapy Dosing
in Patients with Non-Small Cell Lung Cancer IIIB
Lisa Charlotte Thiesing 1; Norman Karg 1; Wolfgang Brückl 2;
Dieter Würein 2; Joachim Ficker 2; Wolfgang Parsch 2
1Paracelsus Medizinische Privatuniversität, Nürnberg
2Klinik für Innere Medizin 3, Schwerpunkt Pneumologie, Universitätsklinik der
Paracelsus Medizinischen Privatuniversität, Klinikum Nürnberg
Purpose: Dose reductions in chemotherapy occur frequently due to vari-
ous reasons. e ubiquitous opinion is that dose reductions favor a nega-
tive outcome. However, there are only few studies that test this opinion in
respect to lung cancer patients. e aim of this retrospective single-center
study is to identify the most common predictors of dose reductions in
NSCLC IIIB patients and to evaluate the eects thereof.
Methods: e study includes 132 patients treated at the Klinikum Nürn-
berg between 2008 - 2015. Predictors of dose reductions were evaluated
using uni- and multivariate methods and survival statistics were analyzed
using Kaplan-Meier and logrank method.
Results: 48% of the patients (n = 63) experienced dose reductions. Male
gender (p = 0.029), age (p = 0.042), comorbidities (CCI) (p = 0.00) and
palliative intent (p = 0.021) were identied as predictors of initial dose
reductions. Initial dose reductions were independent of ECOG status
and initial laboratory values. Dose reductions later in chemotherapy were
linked to hematologic toxicities. e most common hematotoxicites were
leucopenia (45%) and bi-/pancytopenia (23%). 59% of patients with leu-
kopenia and 33% of patients with bi-/pancytopenia had chemotherapeu-
tic doses reduced consecutively. e comparison between patients with
and without dose reduction showed no signicant dierence in overall
survival (OS) (p = 0.598) and progress-free survival (PFS) (p = 0.340). e
OS of patients with reduced doses was 18.86 (± 18.65) vs. 17.51 (± 16.61)
months and PFS was 15.03 (± 18.14) vs. 12.71 (± 17.60) months.
Conclusions: is study supports the view that hematotoxicities are con-
sidered the most serious side eects. In particular, leukopenia was related to
frequent dose reductions. Contrary to expectations, a reduction in chemo-
therapy dosage did not seem to be associated with a worse prognosis. A pos-
sible explanation is that most studies focus on chemotherapy-sensitive tumor
types. In addition, when several cycles of chemotherapy were performed indi-
vidual dose reduction only slightly inuenced the cumulative dose.
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Index
2018
779
Predictive and Prognostic Role of Pretherapeutic
Bodyplethymography in SCLC Patients
Lilli Lmpert; Amanda Tufman; Diego Kaumann-Guerrero
Hospital of the University of Munich (LMU), Department of internal medicine V,
München, Deutschland
Purpose: About 15 % of all newly diagnosed lung cancers are Small Cell
Lung Cancers (SCLC). Despite intensive research in the last 20 years no
relevant improvement of survival has been achieved for these patients.
Estimation of prognosis is essential for treatment planning and patient
guidance. Lung function testing including bodyplethymography and
measurement of diusion capacity has been shown to be a predictive and
prognostic marker in several malignancies. In this context, this project
aims at investigating the predictive and prognostic role of lung function
testing in SCLC patients.
Methods: 209 SCLC patients diagnosed and treated at a German tertiary
care lung cancer were analysed regarding anthropomorphic characteris-
tics. Pretherapeutic lung function tests (spirometry, bodyplethymography
and diusion capacity) were analysed regarding their impact on response
to rst line treatment and survival. Descriptive and comparative uni- and
multivariate analyses were performed
Results: Pretherapeutic elevated values of total lung capacity as well as
residual volume are signicantly associated with rst line treatment fail-
ure and early mortality. Airway obstruction did not show any signicant
impact of treatment response or survival.
Conclusions: Emphysematic lung disease and hyperination seemed to
be a negative pretherapeutic marker regarding treatment response and
survival. ese easy to obtain and cost-eective parameters allow an addi-
tional prognostic estimation in patients with SCLC. us, pretherapeutic
bodyplethymography should be performed in pretherapeutic assessment
of SCLC patients rather than sole spirometry.
Disclosure Statement: No conicts of interest
780
Inammational Scores Predict Survival in Advanced Lung
Cancer Patients
Philipp Habisch; Amanda Tufman; Rudolf Maria Huber;
Diego Kaumann-Guerrero
Divison of Respiratory Medicine and Thoracic Oncology, Department of Internal
Medicine V and Thoracic Oncology Centre Munich, Ludwig-Maximilians-
Universität, München, Deutschland
Purpose: Newly found correlations between inammation and lung can-
cer have expanded the possibilities for patient therapy and prognosis.
Prognostic scores such as mGPS, CAR, NLR, MLR, PLR, SII, LIPI, PIL or
PNI have already proven their validity in the prognosis of patients.
Methods: We retrospectively analyzed 130 lung-cancer-patients treated
at a German tertiary care lung cancer center between 2015 and 2016. We
extracted data sets from electronic records, analyzed anthropometric data,
pre-therapeutic blood values and prognostic scores. Discriminant analy-
sis was performed to predict Overall Survival (OS) and Progression Free
Survival (PFS).
Results: For PFS the factors albumin (p<0,001), clinical response
(p<0,001), CAR (p<0,001), CRP (p<0,001), ECOG-PS (p<0,001), MCV
(p<0,001), mGPS (p<0,001), MLR (p<0,001), PIL (p<0,001), platelets
(p=0,001), LDH (p=0,003), LIPI (p=0,003), lymphocytes (p=0,018),
NLR (p=0,023), PLR (p=0,026), protein (p=0,035), sex (p=0,035) und SII
(p<0,044) were signicant. Signicant prognostic factors of the OS proved
to be Albumin (p<0,001), clinical response (p<0,001), CRP (p<0,001),
ECOG-PS (p<0,001), LDH (p<0,001), LIPI (p<0,001), MCV (p<0,001),
mGPS (p<0,001), PIL (p<0,001), CAR (p=0,002), protein (p=0,002), MLR
(p=0,009), platelets (p=0,017), PNI (p=0,034) and a found driver muta-
tion (p=0,048) in a univariate analysis. In a multivariate analysis MCV,
protein, MLR and PIL were found as independent predictors for OS.
Conclusions: New, inammation-based prognosis scores have shown that
they can be used to make reliable and independent statements about the
prognosis of patients with advanced lung cancer. Since they can be calcu-
lated easily and cost-eectively, they are an ideal complement to classical
prognostic parameters.
Disclosure Statement: Declarations of interest: none; this research did not receive
any specic grant from funding agencies in the public, commercial, or not-for-
prot sectors.
797
Development of ADrug-RelatedCase-Finding Algorithm for
Identifying Patients with NSCLC and SCLC in a German Claims
Database
Sina Neugebauer 1; Frank Griesinger 2; Sabine Dippel 3;
Stephanie Heidenreich 1; Detlef Chruscz 4; Sebastian Lempfert 5;
Peter Kaskel 1
1MSD SHARP & DOHME GMBH, Haar, Deutschland
2Pius Hospital, University Medicine Oldenburg, Dept. Hematology and
Oncology, University Dept. Internal Medicine-Oncology, Oldenburg,
Deutschland
3MSD Merck Sharp & Dohme AG, Luzern, Schweiz
4CONVEMA Versorgungsmanagement GmbH, Berlin, Deutschland
5HCSL Healthcare Consulting, Norderstedt, Deutschland
Purpose: In total,80–85%ofalllung cancer (LC)are classied as non-
small cell LC (NSCLC) and the remaining 15–20% as small cell LC
(SCLC).Histological ndingsare not included withinICD.
Methods: Aim of thisretrospective surveybased onclaimsdataof the
InGef databasewas tond analgorithm to separate NSCLCfrom SCLC
cases. eanalysis period was2015/16.LCpatients were identied based
on ICD-10 codes C33.& C34.
Results: An analysis population of 3.972 primary LC cases was identied.
Since it is not possible to determine the tumor type ofLCwith the help of
the ICD, in this analysis an attempt was made to assign each case based
on the drug therapy (tx) received. Many of the drugs and its combinations
are only approved or prescribed for the tumor of one or the other cell type.
If no dierentiation was possible, the tumor was classied “undieren-
tiated.e following drugs weredocumented:(i)NSCLC:5-uoruracil,
avelumab, cetuximab, ipilimumab, folic acid, gemcitabine, mitomycin,
nab-paclitacel, paclitaxel, pemetrexed, vinorelbine, atezolizumab, beva-
cizumab, necitumumab, nivolumab, pembrolizumab, afatinib, ceritinib,
crizotinib, dabrafenib, erlotinib, getinib, nintedanib, osimertinib, treme-
tinib.(ii)SCLC: irinotecan, liposomal irinotecan, trofosfamid, carbopla-
tin, cyclophosphamide, doxorubicin, epirubicin, etoposide, ifosfamid,
lomustin, topotecan, vincristin.Cisplatin is licensed and prescribed for
both LC entities. For carboplatin, an o-label allowance for NSCLC exists.
780of the cases could be allocated to NSCLC, and253 toSCLC, respec-
tively, but 2.939 cases had to be classied“undierentiated.
Conclusions: is case-nding algorithm is a starting point to separate
between NSCLC and SCLC based on drugs prescribed. However; a lot
of patients remain undierentiated.Reasons arethe wide range of ap-
provals of older chemotx;o label useand undetected coding errors. An
amendment of the DRG System; e.g.; more specic LC codes for NSCLC
and SCLC; is suggested to allow for more specic LC research based on
German claims data.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 127
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2018
Index
2018
Lymphoma and Plasma Cell Disorders
Vorträge
236
Elevate Tn Phase 3 Study of Acalabrutinib Plus Obinutuzumab
or Acalabrutinib Monotherapy vs Chlorambucil Plus
Obinutuzumab (ClbO) in Subjects with Previously Untreated
Chronic Lymphocytic Leukemia (CLL)
Uwe Martens 1; Je Sharman 2; Versha Banerji 3; Laura Maria Fogliatto 4;
Yair Herishanu 5; Talha Munir 6; Renata Walewska 7; George Follows 8;
Karin Karlsson 9; Paolo Ghia 10; Gillian Corbett 11; Patricia Walker 12;
Miklos Egyed 13; Wojciech Jurczak 14; Gilles Salles 15; Ann Janssens 16;
Florence Cymbalista 17; William Wierda 18; Steven E. Coutre 19;
John M. Pagel 20; Alan P. Skarbnik 21; Manali Kamdar 22; Raquel Izumi 23;
Veerendra Munugala 23; Priti Patel 23; Min Hui Wang 23; Soa Wong 23;
Jennifer Woyach 24; John Byrd 24
1Klinik für Innere Medizin III, SLK-Kliniken Heilbronn GmbH / Klinikum am
Gesundbrunnen, Heilbronn, Deutschland
2Willamette Valley Cancer Institute, Eugene, OR, United States
3Department of Biochemistry & Medical Genetics, University of Manitoba,
Research Institute in Oncology and Hematology, Winnipeg, Kanada
4Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre, RS, Brasilien
5Department of Hematology, Tel-Aviv Sourasky Medical Center and Sackler
School of Medicine, Tel-Aviv University,, Tel Aviv, Israel
6Haematological Malignancy Diagnostic Service (HMDS), St James’s Institute of
Oncology, Leeds, United Kingdom
7Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, United
Kingdom
8Department of Haematology, Addenbrookes Hospital NHS Trust, Cambridge,
United Kingdom
9Department of Haematology, Oncology and Radiophysics, Skåne University
Hospital, Lund, Schweden
10Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele, Milano,
Italien
11Department of Medicine, Tauranga Hospital, Tauranga, Neuseeland
12Department of Haematology, Oncology and Radiophysics, Alfred Health-
Monash University, Melbourne, Victoria, Australien
13Department of Hematology, Somogy County Mór Kaposi General Hospital,
Kaposvár, Ungarn
14Department of Hematology, Jagiellonian University Medical College, Krakow,
Poland
15Hospices civils de Lyon, centre hospitalier Lyon Sud, service d’hématologie
clinique, Pierre-Bénite, Frankreich
16Hematology Department, University Hospitals Leuven, Leuven, Belgien
17Bobigny: Hématologie, CHU Avicennes, Bobigny, Frankreich
18Department of Leukemia, University of Texas M.D. Anderson Cancer Center,
Houston, TX, United States
19Stanford University School of Medicine, Stanford, CA, United States
20Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer
Institute, Seattle, WA, United States
21Department of Medicine, John Theurer Cancer Center, Hackensack University
Medical Center, Hackensack, NJ, United States
22Division of Hematology, Hematologic Malignancies and Stem Cell
Transplantation, University of Colorado Cancer Center, Aurora, CO, United States
23Acerta Pharma
24The Ohio State University Comprehensive Cancer Center, Columbus, OH,
United States
Purpose: Acalabrutinib is a highly selective, potent, covalent Bruton
tyrosine kinase inhibitor that has shown clinical benet in patients with
R/R as well as treatment-naïve (TN) CLL. ELEVATE-TN (ACE-CL-007,
NCT02475681), a randomized, multicenter, open-label, phase 3 study
is evaluating the safety and ecacy of acalabrutinib in combination
with obinutuzumab or acalabrutinib monotherapy vs ClbO in TN CLL
patients.
Methods: 535 TN patients with CLL were randomized (1:1:1) into three
arms. Patients in the rst arm received chlorambucil (orally, 0,5 mg/kg at
d1 and 15 of cycle 1 to 6) in combination with obinutuzumab (IV, 100mg
on d1, 900mg on d2, 1000mg on d8 and d15 of cycle 1, 1000mg d1 of cycle
2 to 6). Patients in the second arm received acalabrutinib (orally, 100mg
twice daily until disease progression) in combination with obinutuzumab.
Patients in the third arm received acalabrutinib monotherapy. e prima-
ry endpoint was progression-free survival (PFS) in the acalabrutinib and
obinutuzumab arm compared to the ClbO arm, assessed by an indepen-
dent review committee (IRC), and a key secondary endpoint was IRC-as-
sessed PFS in the acalabrutinib monotherapy arm compared to the ClbO
arm. Other secondary endpoints include objective response rate, time to
next treatment, incidence of adverse events and overall survival.
Results: Data for the primary endpoint and key secondary endpoints
based on a pre-specied interim analysis will be included. e trial has
met its primary endpoint; acalabrutinib in combination with obinutu-
zumab demonstrated a statistically-signicant and clinically-meaningful
improvement in PFS when compared with the chemotherapy-based com-
bination of ClbO. e trial also met a key secondary endpoint showing
acalabrutinib monotherapy achieved a statistically-signicant and clini-
cally-meaningful improvement in PFS compared to ClbO. e safety and
tolerability of acalabrutinib was consistent with its established prole.
Conclusions: Forthcoming; based upon unblinded data results.
Reference:
1. AstraZeneca press release 06/06/19
Poster
115
Collection and Utilization of Hematopoietic Stem Cell
Products in Multiple Myeloma
Felix Krummradt 1; Sandra Sauer 1; Patrick Wuchter 2; Petra Pavel 3;
Eva Klein 1; Anita Schmitt 1; Mark Kriegsmann 4; Karin Jordan 1;
Carsten Müller-Tidow 1; Hartmut Goldschmidt 1, 5; Mathias Witzens-Harig 6;
Katharina Kriegsmann 1
1Universitätsklinikum Heidelberg, Medizinische Klinik V, Heidelberg,
Deutschland
2Medizinische Fakultät Mannheim, Institut für Transfusionsmedizin und
Immunologie, Mannheim, Deutschland
3Blutspendezentrale IKTZ Heidelberg, Stammzell-Labor, Heidelberg,
Deutschland
4Universitätsklinikum Heidelberg Pathologisches Institut: Allgemeine
Pathologie und pathologische Anatomie, Heidelberg, Deutschland
5Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland
6Universitätsklinikum Heidelberg, Heidelberg, Deutschland
Purpose: High-dose (HD) chemotherapy and autologous blood stem-
cell transplantation (ABSCT) is the standard of care in multiple myeloma
(MM) for transplant-eligible patients. Up to three HD/ABSCTs may be
given during the course of disease, including late-onset relapse.1 ere-
fore, many transplant centers routinely collect more than one peripheral
blood stem cell (PBSC) gra.2 However, subsequent HD/ABSCTs are of-
ten not performed for a variety of reasons.3
Methods: e collection, storage and disposal practice of PBSC products
in a large cohort of MM patients (n=1,114) during a 12-year period was
analyzed (minimum follow-up time 7 years).
Results: e median number of sucient PBSC transplants per patient
was 3 (range 0-6), those were stored in a median of 3 (range 1-11) cryo-
preserved bags (overall n=3,644). 95% of all patients (n=1,059) underwent
at least one HD/ABSCT. However, more than one ABSCT was performed
in 48% (n=532) of patients. Only a small proportion of PBSC bags (3%,
n=109) was used aer a storage of >5 years. Overall, 23% (n=830) of the
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2018
products were discarded and 16% (n=566) were kept in storage until ref-
erence date (March 2019).
Conclusions: We identied considerable discrepancies between the col-
lection/storage and utilization of PBSCs. is is on the one hand associ-
ated with signicant eorts and costs, on the other hand the disposal may
raise legal and ethical questions. We therefore implemented comprehen-
sive guidelines for systematic re-evaluation of stored PBSC gras at our
institution.
References:
1. Chute JP. Autologous Stem Cell Transplantation for Multiple Myeloma: Unde-
rutilized but Highly Eective. J Natl Cancer Inst 2018.
2. Lisenko K et al. Storage Duration of Autologous Stem Cell Preparations Has
No Impact on Hematopoietic Recovery aer Transplantation. BBMT 2017.
3. Phipps C et al. Utilization of stored autologous PBSCs to support second auto-
logous transplantation in multiple myeloma patients in the era of novel agent
therapy. BMT 2015.
156
Simultaneous Occurrence of Castlemans Disease and
Plasmocytoma with Progression Into Multiple Myeloma
Associated with POEMS Syndrome
A. Wyrwa 1; U. Rüddel 1; O. Yomade 1; W. Franz 2; H.H. Wacker 2; A.
Hochhaus 1; K.G. Schrenk 1
1Klinik für Innere Medizin II, Abteilung Hämatologie und Internistische
Onkologie, Universitätsklinikum Jena , Jena, Deutschland
2Institut für Hämopathologie Kiel, Kiel, Deutschland
Purpose: Castlemans disease (CD) is a rare heterogeneous group of
lymphoproliferative disorders. We present an unusual case of a patient
with simultaneous CD and plasmocytoma followed by progression into
multiple myeloma with POEMS syndrome and discuss the diagnostic
criteria as well as the treatment options.
Methods: Case report and review of the literature.
Results: A 67-year old woman presented with weight loss, generalized
sensory neuropathic pain, disseminated hemangiomas of the skin and
enlarged mediastinal lymph nodes. On histology the typical morphology
of CD with hyperplastic lymphoid follicles in combination with a lambda
light chain plasmocytoma was found. Additionally monoclonal gammop-
athy of uncertain signicance of the lambda light chain type was demon-
strated. In the bone marrow plasma cells were below 10 %. e criteria for
POEMS (polyradiculoneuropathy, organomegaly, endocrinopathy, mono-
clonal plasma cell disorder and skin changes) syndrome were initially not
met, due to the absence of peripheral neuropathy on electrophysiological
studies. VEGF serum levels were increased with > 1000 pg/ml (NR <445
pg/ml). HIV and HHV8 were negative. Because of the multicentric pre-
sentation of CD a systemic therapy with the anti-Il-6 antibody siltuximab
was started. Aer 13 months of treatment the patient experienced multi-
ple cerebral thrombembolic events. At the same time progressive disease
was diagnosed and treatment was changed to immunochemotherapy with
6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincris-
tine, prednisone). During the 6th cycle of R-CHOP lambda light chains
increased noticeably. Restaging with lymphadenectomy proved a good
response with complete remission of CD. However bone marrow biopsy
showed progression into multiple myeloma with an increase of plasma
cells up to 60 % and electrophysiological studies revealed peripheral neu-
ropathy corresponding to POEMS syndrome.
Conclusions: is unusual case demonstrates the diagnostic challenges as
well as treatment options in Castleman´s disease and POEMS syndrome.
183
Ascend Phase 3 Study of Acalabrutinib vs Investigator’s
Choice of Rituximab Plus Idelalisib (IDR) or Bendamustine
(BR) in Patients with Relapsed/Refractory (R/R) Chronic
Lymphocytic Leukemia (CLL)
Holger Hebart 1; Paolo Ghia 2; Wojciech Jurczak 3; Andrzej Pluta 4;
Malgorzata Wach 5; Daniel Lysak 6; Tomas Kozak 7; Martin Šimkovič 8;
Polina Kaplan 9; Irina Kryachok 10; Arpad Illes 11; Javier De la Serna 12;
Sean Dolan 13; Philip Campbell 14; Gerardo Musuraca 15; Abraham Jacob 16;
Eric Avery 17; Priti Patel 17; Cheng Quah 18; Wei Liang 18; Jae Hoon Lee 19
1Kliniken Ostalb, Stauferklinikum Schwäb. Gmünd, Zentrum Innere Medizin/
Hämatologie/Onkologie, Mutlangen, Deutschland
2Ospedale San Raaele, Unita Tumori Linfoldi, Dipartimento di Oncoematologia,
Milano, Italien
3Malopolskie Centrum Medyczne, Malpolskie, Poland
4Szpital Specjalistyczny w Brzozowie, Podkarpacki Osrodek Onkologiczny im.
Ks.B. Markiewicza, Podkarpackie, Poland
5Samodzielny Publiczny Kliniczny nr 1 w Lublinie, Klinika Hematoonkologii i
Transplantacji Szpiku, Lubelskie, Poland
6Fakultni Nemocnice Plzen, Plzen-Lochotin, Tschechien
7Fakultni Nemocnice Kralovske Vinohrady, Interni hematologicka klinika,
Prahna, Tschechien
8V.Interni hematologicka klinika, Vychodocesky Kraj, Tschechien
9Dnipropetrovsk City Multield Cöinical Hospital Number 4, City Hematology
Center, Dnipropetrovsk, Ukraine
10National Cancer Instutue, Kiev, Ukraine
11Debreceni Egyetem Belgyogyaszai Klinika, Hematologiai Tanzek, Hajdu-Bihar,
Ungarn
12Hospital Universitario 12 de Octubre Servicio de Hematologia, Centro de
Actividades Ambulatorias, Planta 3, Area D, Madrid, Spanien
13Saint John Regional Hospital, Saint John NB E2L 4L2, Kanada
14Barwon Health, The Andrew Love Cancer Centre, Barwon Health, Geelong,
Australien
15Istituto Scientico Romagnolo per lo Studio e la Cura dei Tumori, U.O. di
Oncologia Medica - Oncoematologia, Forli-Cesena, Italien
16The Royal Wolverhampton NHS Trust, New Cross Hospital, Wolverhampton,
United Kingdom
17Nebraska Hematology Oncology, Lincoln, NE 68506
18Gachon University Gil Medical Center, Incheon, Korea
Purpose: In this randomized, global, multicenter, open-label Phase 3
study (CL-309; ASCEND; NCT02970318), the ecacy and safety of aca-
labrutinib, a highly selective, potent, covalent Bruton tyrosine kinase in-
hibitor, was evaluated vs investigator’s choice of IdR or BR in R/R CLL.
Methods: Eligible patients (pts) with R/R CLL were randomized 1:1 to
100 mg oral acalabrutinib BID until progression vs IdR (Id 150 mg oral
BID and up to 8 IV infusions of R [375 or 500 mg/m2]) or BR (70 mg/m2
IV B on d1 and 2 and R [375 or 500 mg/m2 IV] on d1 for up to 6 cycles).
e primary endpoint was progression-free survival (PFS) assessed by in-
dependent review committee (IRC).
Results: 310 pts were randomized to acalabrutinib (n=155) or IdR/BR
(n=155 [IdR, n=119; BR, n=36]); median age was 67 y (range, 32-90).
At a median follow-up of 16.1 mo, acalabrutinib signicantly prolonged
IRC-assessed PFS vs IdR/BR (median NR vs 16.5 mo; HR 0.31, 95% CI
0.20-0.49, P<.0001). PFS rates at 12 mo were 88% with acalabrutinib and
68% with IdR/BR. PFS improvement with acalabrutinib (vs IdR/BR) was
seen across subgroups including del(17p), TP53 mutation and Rai stage.
IRC-assessed ORR was not signicantly dierent with acalabrutinib vs
IdR/BR (81% vs 75%, respectively; p<.22). 12-mo OS rates were 94% and
91% (with 15 and 18 deaths) for acalabrutinib and IdR/BR, respective-
ly. 23% of pts randomized to IdR/BR crossed over to receive subsequent
acalabrutinib. Grade ≥3 AEs with acalabrutinib (≥5%) were neutropenia
(16%), anemia (12%) and pneumonia (5%); with IdR (≥15%), neutrope-
nia (40%) and diarrhea (24%); with BR (≥5%), neutropenia (31%), anemia
(9%) and constipation (6%). AEs of interest were atrial brillation (5.2%
of pts on acalabrutinib vs 3.3% on IdR/BR), bleeding AEs (26% vs 7.2%;
including major hemorrhage [1.9% vs 2.6%]), Grade ≥3 infections (15%
vs 24%), and 2nd primary malignancies (excluding NMSC; 6.5% vs 2.6%).
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2018
Conclusions: Acalabrutinib monotherapy signicantly improved PFS
with a more tolerable safety prole compared with IdR/BR in pts with
R/R CLL.
Reference:
1. EHA Library. Ghia P. Jun 16; 2019; 273259; LB2606
185
Treatment Reality of Myeloma Patients 2012-2018 in Germany
Rudolf Weide 1; Holger Schulz 2; Lothar Müller 3; Oswald Burkhard 4;
Ute Braun 5; Tilman Steinmetz 6; Peter Ehscheidt 7; Ingo Tamm 8;
Bernhard Rendenbach 9; Stefan Feiten 10
1Praxis für Hämatologie und Onkologie, Koblenz, Deutschland
2pioh - Praxis Internistische Onkologie und Hämatologie, Frechen/Köln,
Deutschland
3Onkologie UnterEms, Leer/Papenburg/Emden, Deutschland
4Internistische Gemeinschaftspraxis Hämatologie, Onkologie, Palliativmedizin,
Worms, Deutschland
5Gemeinschaftspraxis für Hämatologie und Onkologie, Ludwigshafen,
Deutschland
6MV-Zentrum für Onkologie und Hämatologie, Köln, Deutschland
7Onkologische Praxis Dr. Ehscheidt, Neuwied, Deutschland
8Onkologische Schwerpunktpraxis Kurfürstendamm, Berlin, Deutschland
9Praxis für Hämatologie, Onkologie und Nephrologie, Trier, Deutschland
10Institut für Versorgungsforschung in der Onkologie, Koblenz, Deutschland
Purpose: Survival of Multiple Myeloma (MM) patients has improved
in prospective randomized trials. Real world data concerning treatment
and outcome from unselected patients who receive routine care are not
known.
Methods: Multicentre retrospective analysis of 1,000 unselected MM
patients who were treated between 01/2012 and 12/2018 in 9 communi-
ty-based oncology group practices in Germany. Data were extracted from
patient les into a database and analyzed statistically using SPSS.
Results: So far 770 patients have been documented, 45% were female, 55%
male. Median age was 69 years (25-92). 651 patients (85%) fullled CRAB
criteria for cytoreductive treatment. 1st line treatment consisted of bor-
tezomib+dexamethasone (VD) in 15%, bortezomib+melphalan+dexa-
methasone (VMP) in 14%, bortezomib+cyclophosphamide+dexametha-
sone (VCD) in 10% and lenalidomide+dexamethasone (Rd) in 6%. 23%
received other therapy combinations. 32% were treated with high dose
melphalan and stem cell transplantation (SCT). 2nd line therapy consisted
of Rd in 26%, VD in 13%, VMP in 6%, thalidomide+dexamethasone in
6%, VCD in 5%, carlzomib+lenalidomide+dexamethasone (KRd) in 4%
and bendamustine+dexamethasone in 4%. 13% had high dose melphalan
and SCT. 3rd line therapy consisted of Rd in 25%, VD in 10%, VMP in
5%, VCD in 4%, KRd in 3%, daratumumab in 3%, lenalidomide+dara-
tumumab+dexamethasone in 3% and pomalidomide+dexamethasone in
3%. Median overall survival (OS) of the whole cohort was 95.4 months
(0.6-304.8). OS was strongly dependent on age, comorbidities and ECOG
performance status. Median OS of the age cohorts 25-60, 61-70, 71-75 and
76-92 was 146.5 (2.1-340.8), 112.8 (0.6-201.5), 80.8 (0.6-199.8+) and 52.6
(1.2-124.6) months respectively (p<.001).
Conclusions: MM patients who are treated in routine care receive therapy
as suggested by international recommendations. Survival has improved
compared to historical controls and is strongly dependent on age, comor-
bidities and performance status.
Disclosure Statement: All authors report no conicts of interest
266
Obesity is Associated with an Impaired Survival in Lymphoma
Patients Undergoing Autologous Stem Cell Transplantation
Julius Enßle 1; Sebastian Scheich 1; Victoria T. Mücke 2; Fabian Acker 1;
Lukas Aspacher 1; Sebastian Wolf 1; Anne C. Wilke 1; Sarah Weber 1;
Uta Brunnberg 1; Hubert Serve 1; Björn Steen 1
1Medizinische Klinik II - Hämatologie/Medizinische Onkologie,
Universitätsklinikum Frankfurt, Frankfurt, Deutschland
2Medizinische Klinik I - Gastroenterologie/Hepatologie, Universitätsklinikum
Frankfurt, Frankfurt, Deutschland
Purpose: In relapsed and refractory lymphomas, autologous hematopoi-
etic stem cell transplantation (auto-HSCT) provides a possibly curative
treatment option.1,2 Obesity displays an emerging epidemic risk factor for
global mortality and is associated with an increased mortality in cancer
patients.3,4 To date, there is no uniform data on the impact of obesity on
the outcome of lymphoma patients undergoing auto-HSCT.
Methods: We conducted a retrospective single-center study assessing 119
lymphoma patients who underwent auto-HSCT. Overall survival (OS)
served as primary endpoint whereas progression free survival (PFS), cu-
mulative incidence of non-relapse related mortality (NRM) and cumula-
tive incidence of relapse were analyzed as secondary endpoints.
Results: Obese patients (BMI≥30) unveiled a signicant lower OS (45.3%
vs. 77.9%; p=0.005) and PFS (29.8% vs. 67.2%; p<0.001) compared to
non-obese patients at 48 months. e cumulative incidence of NRM dis-
played no signicant dierences while the cumulative incidence of relapse
was signicantly increased in patients with BMI≥30 (66.2% vs. 21.5%;
p<0.001). ere was no signicant dierence in OS between patients with
a BMI<25 and overweight patients (BMI 25-30; 76.1% vs. 80.9%; p=0.585)
whereas patients with BMI≥30 exhibited signicant lower OS when com-
pared to either of both groups (76.1% vs. 45.3%; p=.0.021 and 80.9% vs.
45.3%; p=0.010). Furthermore, in a multivariate analysis, obesity was
identied as an independent risk factor for death (HR 2.231; 95% CI 1.024
to 4.860; p=0.043).
Conclusions: In the present study, we demonstrate that obesity is asso-
ciated with an impaired outcome in lymphoma patients undergoing au-
to-HSCT. Further studies are needed to evaluate the reasons for the higher
relapse rate causing higher mortality in obese patients.
References:
1. Hutchings M, et al. Ann Oncol. 2018
2. Philip T, et al. N Engl J Med. 1995
3. Ng M, et al. Lancet. 2014
4. Renehan AG, et al. Lancet. 2008
Disclosure Statement: e authors declare no conict of interest.
302
Pomalidomide, Cyclophosphamide and Dexamethasone (PCD)
is an Eective Salvage Regimen for Multiple Myeloma (MM)
Patients Relapsed and/or Refractory to Daratumumab
Annamaria Brioli 1, 2; Katia Mancuso 3; Thomas Ernst 1; Inken Hilgendorf 1;
Elena Zamagni 3; Florian Heidel 1; Thomas Stauch 1; Andreas Hochhaus 1;
Marie von Lilienfeld-Toal 1
1Universitätsklinikum Jena, Klinik für Innere Medizin II, Abt. Hämatologie und
Internistische Onkologie, Jena, Deutschland
2Universitätsklinikum Jena, Else Kröner Forschungskolleg AntiAge, Jena,
Deutschland
3Università di Bologna, Policlinico S.Orsola-Malpighi, Istituto di Ematologia e
Oncologia Medica, L. e A. Seràgnoli“, Bologna, Italien
Purpose: Daratumumab (dara) alone or in combination with lenalido-
mide (daraRd) or bortezomib (daraVd) is approved for the treatment of
relapsed and/or refractory MM patients (pts). However, treatment options
for pts progressing on dara are limited, and little data are available on the
ecacy of salvage treatment aer dara.
Methods: e aim was to evaluate the ecacy of PCD as salvage therapy
aer dara. Progression free survival (PFS) and overall survival (OS) were
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2018
Index
2018
calculated from the start of PCD. e median follow-up was 16 months
(mo).
Results: irteen pts treated at Jena University Hospital and at the Serag-
noli Institute of Hematology in Bologna who received at least 1 cycle of
PCD aer dara-failure were included. Median age at the start of PCD was
64 years (range 51-84). ree pts had extramedullary (EM) disease. e
median number of previous lines of therapy was 5 (range 2-9). Twelve pts
had previously been treated with melphalan, 2 pts had received allogene-
ic SCT. All patients had previously received IMiDs (12/13 lenalidomide,
4/13 thalidomide), with 11 pts progressing on IMiD therapy. Twelve pts
received bortezomib and 7/13 carlzomib; 9/12 pts were refractory to
proteasome inhibitors. Dara combinations were: 6 pts dara alone, 5 pts
daraRd and 2 pts daraVd. Seven pts (including 2 pts with EM disease)
had a disease refractory to dara. e median daily dose of pomalidomide
was 4 mg (range 1-4), median doses per cycle of cyclophosphamide was
700 mg/m2 (range 0-1800) and of dexamethasone 160 mg (range 0-320).
e median number of cycles of PCD was 5 (range 1-31); 6 patients are
still on treatment. Overall response rate (≥PR) to PCD was 62% (8/13),
including 2 pts with VGPR and 2 pts with CR. Of the 3 pts with EM dis-
ease, 1 achieved a CR and 1 a minimal response. Responses occurred aer
a median of 2 cycles (range 1-5). Median duration of response was 3 mo
(95% CI 0-9), median PFS and OS were 9 (95% CI 3-15) and 16 (95%
CI 9-23) mo, respectively. Toxicity of grade ≥3 was limited and mainly
hematologic (6/13 pts).
Conclusions: PCD is an eective regimen for dara refractory pts, includ-
ing those with EM disease.
361
Rare Lymphomas – Epidemiology from the Munich Cancer
Registry
Anne Schlesinger-Raab 1; Renate Eckel 1; Kathrin Halfter 1;
Gabriele Schubert-Fritschle 2; Jutta Engel 2
1Tumorregister München am Klinikum der Universität München, Institut für
Medizinische Informationsverarbeitung Biometrie und Epidemiologie,
Ludwig-Maximilians-Universität München, München, Deutschland
2Tumorregister München, Bayerisches Kebsregister - Regionalzentrum
München (LGL) am Klinikum der Universität München, Institut für Medizinische
Informationsverarbeitung Biometrie und Epidemiologie , Ludwig-Maximilians-
Universität, München, Deutschland
Purpose: Rare cancers are dened as cancers with an incidence of less
than 6/100,000. In total they represent 22% of the new cancer cases. Lym-
phomas in total are not rare, but they fragment into many dierent enti-
ties which therefore count as rare. e population-based data herein is
presented to weigh in on the results of randomized clinical trials and to
clarify expectations in the treatment of sporadic diagnoses.
Methods: Nine dierent rare lymphoma entities registered in the catch-
ment area of the Munich Cancer Registry (MCR) 1998-2016 were selected
for presentation: lymphocyte predominant Hodgkin lymphoma, hairy cell
leukemia, Mantle cell lymphoma, Burkitts lymphoma, MALT lymphoma,
M. Waldenström, primary lymphoma of the central nerve system, cutane-
ous T-cell lymphoma, and peripheral mature T-cell lymphoma. Incidenc-
es, distributions of patient and tumor characteristics, and survival were
computed per entity, sex, and period of initial diagnosis.
Results: e incidences (ASR ES) range between 0.6/100,000 in Mantle
cell lymphoma and 0.15/100,000 in lymphocyte predominant Hodgkins
lymphoma. Men account for 62% of all patients. e median age diers
between 44 years in Burkitt’s lymphoma and 68 years in Morbus Walden-
ström. e 5-year relative survival (as estimation for cancer specic sur-
vival) lies between 35.6% in primary CNS lymphoma and 94.7% in hairy
cell leukemia (94.2% in lymphocyte predominant Hodgkin lymphoma,
61.3% in Mantle cell lymphoma, 64.9% in Burkitts lymphoma, 89.8% in
MALT lymphoma, 82.3% in M. Waldenström, 70.7% in cutaneous T-cell
lymphoma, and 42.4% in peripheral mature T-cell lymphoma). Apart
from MALT lymphoma and lymphocyte predominant Hodgkin lympho-
ma men have a better prognosis than women. A noteworthy improvement
in survival over time cannot be shown.
Conclusions: Incidence; age; and outcome in rare lymphomas vary ex-
tremely. e treatment of rare diseases such as these lymphomas should
be expanded by the knowledge of “real-life” population-based data to ad-
just and deliver the patients’ expectations.
392
The Prospective Intersectoral National Cohort Study Myriam
to Study Characteristics, Treatment and Outcome of Patients
with Multiple Myeloma in Germany
Wolfgang Knauf 1; Monika Engelhardt 2; Christoph Losem 3; Jörg Lipke 4;
Christian Kasper 5; Tanja Medinger 6; Leonora Houet 7; Martina Jänicke 7;
Norbert Marschner 8; Tobias Dechow 9; Hermann Einsele 10
1Centrum für Hämatologie und Onkologie Bethanien, Frankfurt a.M.,
Deutschland
2Universitätsklinikum Freiburg, Freiburg i.Br., Deutschland
3MVZ für Onkologie und Hämatologie im Rhein-Kreis Neuss, Neuss,
Deutschland
4Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund, Deutschland
5Onkologische Schwerpunktpraxis Hof - Medizinisches Versorgungszentrum,
Hof, Deutschland
6iOMEDICO, Freiburg im Breisgau
7iOMEDICO Freiburg, Freiburg i.Br., Deutschland
8Praxis für Interdisziplinäre Onkologie & Hämatologie, Freiburg i.Br.,
Deutschland
9Gemeinschaftspraxis für Hämatologie und Onkologie, Ravensburg,
Deutschland
10Universitätsklinikum Würzburg, Würzburg, Deutschland
Purpose: erapeutic options for multiple myeloma (MM) have markedly
increased over the last decade and a number of new treatments may be ap-
proved in the near future. MYRIAM is a prospective, intersectoral, nation-
al, longitudinal, multicenter cohort study to document patient and disease
characteristics, treatments, course of disease, including clinical and pa-
tient-reported outcomes and consent to perform translational research.
Methods: Between 2017 and 2021 about 2.000 patients with MM giving
informed consent at the start of their rst or second systemic treatment
will be prospectively recruited in 150 dierent sites, including university
and community hospitals and oce-based practices and will be followed
until death or for a maximum of 5 years. Data will be collected in elec-
tronic case report forms with implemented completeness and plausibility
checks, regularly examined by data managers and randomly monitored.
Patient-reported outcomes will be assessed at the time of recruitment, ev-
ery 3 months for the rst 24 months and every 6 months thereaer, for a
maximum of 5 years altogether using the EORTC-QLQ-C30+MY20 and
the Brief Pain Inventory. Patients will be asked to give informed consent
for future translational research of their unused tumor samples. Annu-
al interim analysis will be performed. e study was approved by local
ethics committees and is registered under clinicaltrials.gov (identier:
NCT03308474).
Results: e rst patient was recruited in September 2017. At the time of
abstract submission (August 2019), 788 patients had been recruited in 103
sites. First results on patient and disease characteristics and initial treat-
ments will be presented.
Conclusions: MYRIAM will for the rst time present prospective, inter-
sectoral, longitudinal data on MM patients in Germany. Data will shed
light to the current state of care and allow identication of unmet medical
needs.
Disclosure Statement: None of the authors has declared a conict of interest
regarding the subject of this work.
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2018
524
Diuse Large B-Cell Lymphoma Patient-Derived Xenograft
Models: Establishment and Treatment Study
Aitomi Bittner 1; Bernadette Brzezicha 2; Sophy Denker 1; Nina Thiessen 3;
Clemens A. Schmitt 1, 3, 4, 5, 6
1Charité - University Medical Center, Department of Hematology,
Oncology and Tumor Immunology, Virchow Campus, and Molekulares
Krebsforschungszentrum, Berlin, Deutschland
2Experimental Oncology & Pharmacology Berlin-Buch, Berlin, Deutschland
3Berlin Institute of Health, Berlin, Deutschland
4Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association,
Berlin, Deutschland
5Kepler University Hospital, Department of Hematology and Oncology,
Johannes Kepler University, Linz, Österreich
6Deutsches Konsortium für Translationale Krebsforschung (German Cancer
Consortium), Partner site Berlin, Berlin, Deutschland
Purpose: About 30-40% of the patients diagnosed with diuse large B-cell
lymphoma (DLBCL) will not be cured by standard R-CHOP therapy. De-
spite intense molecular proling eorts, the treatment standard remains
unchanged so far. us, new models such as patient-derived xenogras
(PDX) are pivotal to develop molecularly guided treatment alternatives.
Methods: DLBCL PDX were derived from lymph node extirpations or
core needle biopsies, transplanted subcutaneously into immunodecient
NOG mice, and subsequently passaged to NMRI nu/nu mice. Each gra
was passaged 4 to 5 times to generate a stable model. In addition to histo-
logical analysis, whole genome sequencing (WGS) and RNA sequencing
was performed. Stable PDX models were used for treatment studies.
Results: We successfully established 6 DLBCL PDX models from patients
routinely admitted to our center and exposed to standard induction (i.e.
R-CHO[E]P) or salvage therapy in case of progress, as well as patients
treated within the actively recruiting investigator-initiated trial Imbru-
VeRCHOP (ibrutinib, bortezomib, R-CHOP; PI: Clemens A. Schmitt;
multi-center rst-line trial). We performed WGS and gene expression
proling to monitor lymphoma heterogeneity and clonal evolution at pri-
mary PDX establishment and during subsequent serial passaging. Rem-
iniscent of our ImbruVeRCHOP trial, we conducted a treatment study.
In the cyclophosphamide-resistant models, we were able to show that the
addition of ibrutinib and bortezomib to cyclophosphamide delayed tumor
growth. Next, panel-based targeted re-sequencing will be applied to serial
samples obtained upon treatment exposure to investigate therapy-driven
clonal evolution and emerging drug resistance.
Conclusions: e DLBCL PDX models reect histological and genetic
heterogeneity of the primary DLBCL sample from which they were de-
rived from, and present with varying response patterns to ImbruVeR-
CHOP compounds. Response associations with the clinical outcome of
the respective patients, and with distinct molecular proles will be dis-
cussed at the conference.
640
Non-Interventional Optimob-Study: a Nationwide Evaluation
of Mobilization and Collection of Hematopoietic Stem and
Progenitor Cells in Patients with Multiple Myeloma (MM) and
Lymphoma in Clinical Practice
Nicolaus Kröger 2; Max Bittrich 3; Vladan Vucinic 4; Matthias Grube 5;
Marcus Hentrich 6; Maike de Wit 7; Christian Kunz 8; Bernd Metzner 9;
Andreas Humpe 10
1Universitätsklinikum Hamburg-Eppendorf, Department of Stem Cell
Transplantation , Hamburg, Deutschland
2University Hospital Hamburg-Eppendorf, Department of Stem Cell
Transplantation, Hamburg, Deutschland
3Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik II, Zentrum
Innere Medizin (ZIM), Würzburg, Deutschland
4University Hospital Leipzig, Department of Hematology and Cell Therapy,
Leipzig, Deutschland
5University Hospital Regensburg, Department of Internal Medicine III,
Regensburg, Deutschland
6Rotkreuzklinikum München, Department of Internal Medicine III, München,
Deutschland
7Vivantes Clinic Neukoelln, Department of Hematology, Oncology and Palliative
Medicine, Berlin, Deutschland
8Westpfalz-Klinikum GmbH, Department of Internal Medicine 1, Kaiserslautern,
Deutschland
9Klinikum Oldenburg, Department of Hematology and Oncology, Oldenburg,
Deutschland
10Klinikum der Universität München - Campus Grosshadern , Department of
Transfusion Medicine, Cellular Therapeutics and Hemostasiology, München,
Deutschland
Purpose: Autologous stem cell transplantation (ASCT) remains a stan-
dard therapy for MM and lymphoma in eligible patients (pts). A sucient
yield of stem cells is necessary for a successful ASCT. In clinical routine
est. 15% (1) of pts are classied as poor mobilizers (PM) requesting sever-
al apheresis sessions (aph). Stem cells are mobilized with chemotherapy +
G-CSF +/- plerixafor (PLX) or G-CSF +/- PLX.
Methods: Pts. with MM, Non-Hodgkin lymphoma or Hodgkin lympho-
ma eligible for ASCT are included in OPTIMOB. Mobilization and collec-
tion parameters are documented and analyzed in detail. Primary endpoint
of the study is the proportion of PM pts. reaching ≥ 2 mio CD34+ cells /
kg body weight with the 1st apheresis. Pts. are dened as PM if they did
not reach ≥ 20 CD34+ cells / µL before 1st aph., receive PLX at any time
point, did not reach the initially planned stem cell yield or terminated
collection early due to poor mobilization. It is planned to include 1.500
pts to identify 210 PM pts.
Results: Up to now 189 pts from 16 centers are documented. About two
thirds of pts have MM and one third malignant lymphoma. Mean age is
61 years and 40 % of pts are female. Half of pts are classied as PM (n=39)
and 21 out of 80 pts received PLX + G-CSF +/- chemotherapy for mobili-
zation. Furthermore, 19 AEs were reported incl. 2 SAEs.
Conclusions: is ongoing large prospective observational study evalu-
ates stem cell mobilization rates in pts with MM and lymphoma who are
candidates for ASCT. Updated data will be presented at the meeting.
Reference:
1. Wuchter et al. Biol Blood Marrow Transplant 16: 490-499 (2010)
Disclosure Statement: is study is supported by Sano.
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2018
647
Gender Dierences in Hematological Malignancy: The
Experience of Jena University Hospital
Maria Madeleine Rüthrich 1; Jakob Hammersen 1; Paul La Rosée 2;
Lars-Olof Mügge 3; Andreas Hochhaus 1; Marie von Lilienfeld-Toal 1;
Annamaria Brioli 1, 4
1Universitätsklinikum Jena, Klinik und für Innere Medizin II, Abteilung für
Hämatologie und internistische Onkologie, Jena, Deutschland
2Schwarzwald-Baar Klinikum, Klinik für Innere Medizin II, Onkologie,
Hämatologie, Immunologie, Infektiologie und Palliativmedizin, Villingen-
Schwenningen, Deutschland
3Heinrich-Braun-Klinikum, Innere Medizin III Hämatologie, Onkologie und
Palliativmedizin, Zwickau, Deutschland
4Universitätsklinikum Jena, Else-Kröner Forschungskolleg AntiAge, Jena,
Deutschland
Purpose: Cardiological studies showed that female (F) patients (pts)
might be undertreated. Data in hematological malignancies are lacking.
Methods: Aim was to investigate gender dierences in multiple myelo-
ma (MM) and diuse large B-cell lymphoma (DLBCL) pts treated at one
center. e MM and DLBCL databases were retrospectively interrogated.
Analysis included descriptive statistics and survival analyses.
Results: Pts included were: 655 (MM) and 304 (DLBCL). Median obser-
vation was 48 months (mo) in MM and 41 mo in DLBCL. F were 43%
(MM) and 51% (DLBCL). Median age was 62 years (yr) (MM, range 35-
89) and 65 yr (DLBCL, range 20-92), and similar between F and men (M)
(MM p=.14, DLBCL p=.33)
At diagnosis (dg) MM pts had no dierence in disease risk (p=.49), stage
(p=.52), MM type (p=.62), or bone involvement (p=.79). F had lower Hb
(p<.001), less coronary heart disease (p=.006) and COPD (p<.001). In
DLBCL, pts status and disease stage were similar: ECOG ≥2 p=.99, stage
≥III p=.14, IPI ≥3 p=.64. More F had B symptoms (p=.04).
MM pts had no dierence in therapy (tp) administered (number/type)
at dg or at rst relapse, in overall response rate (ORR, F 71% vs M 72%,
p=.43) and in overall survival (OS, F 83 vs M 72 mo, p=.45, 95% CI [63-
89]). is applies to all age groups. High dose tp (HDT) was not aected
by sex. More F had mucositis grade ≥3 (p=0.001). Progression free surviv-
al (PFS) (F 27 vs M 26 mo, p=0.37, 95% CI [23-29]) and OS from HDT (F
83 vs M 74 mo, p=0.90, 95% CI [59-95]) were similar.
In DLBCL, 257 pts received CHOP-like tp. ere was no dierence in
ORR (F 72% vs M 69%, p=.56) or OS (F not reached (NR) vs. M 83 mo,
p=.89, 95% CI [54-112]). Elderly F (60-79 yr) had R-CHOP14 in 40% vs
58% elderly M (p=.04). ORR (F 77.5% vs M 73%, p=.83), OS (F NR vs M
NR, p=.94) and PFS (F NR vs M 72 mo p=.64, 95% CI [17-127]) did not
dier, but R-CHOP14 was superior to 21 in elderly F (PFS NR vs 18 mo,
p=.007 95% CI [9-28]).
Conclusions: Gender does not impact on biology, tp and outcome of MM
pts. In Dlbcl, data suggests that elderly F might be undertreated with a
possible eect on outcome.
Disclosure Statement: AB received honoraria from Takeda; Celgene; Sano and
Janssen; Travel support from Celgene; Takeda; Janssen and Gilead and research
founding from Celgene; MvLT received travel support and research founding from
Janssen; Celgene; Takeda; Gilead; MSD; Oncopeptides and Novartis; the other
authors have no conict of interest to declare
722
Treatment of Patients WiT Refractory Hodgkin Lymphoma
Nadezda Basara; Nikolai Faber; Helge Menzel; Petra Drewniock;
Xenia Sitskaia; Stefan Lukic
St Franziskus Hospital, Academical Hospital of the UKSH, Internal medicine I,
Flensburg, Deutschland
Purpose: e anti-CD30 immunotoxin brentuximab-vedotin and check-
point inhibitors Nivolumab and Pembrolizumab has being used for re-
fractory HL patients as monotherapy and in dierent combinations.
Methods: is presentation summarizes our experience in the treatment
of refractory HL.
Results: We have treated a total of 8 patients with refractory Hodgkin
Lymphoma with Nivolumab or Brentuximab, 6 men and 2 female, 16 to
56 years of age. All patients had ECOG 0, 3-4 lines of therapy, 5 patients
had previous radiation therapy, and 4 patients have been treated with au-
tologous peripheral blood stem cell transplantation (PBSCT). Previous
allogeneic PBSCT has been performed in one patient, and 4 patients have
been treated with brentuximab-vedotin prior to nivolumab. e patients
have been treated with 1-8 cycles of Nivolumab 3mg/kg b.w. two weekly
according to the recommendation from CHECK Mate 205 Phase II Study.
e overall response was excellent, CR in 4 patients and PR in 3 patients.
In one patient, the treatment with Nivolumab was terminated due to Liver
toxicity Grade 2.
Conclusions: Encouraging durability of response in our patients of 75% at
median follow up of 25 months has been described. e safety prole with
AEs mostly grade 1 or 2 was acceptable. Nivolumab is an important new
therapy in patients with refractory HL.
References:
1. Chen R, Gopal AK, Smith SE et al. 5-year survival and durability results of
Brentuximab-vedotin in patients with relapsed or refractory Hodgkin lympho-
ma. Blood 2016; 128:1562
2. Armand P, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classic
Hodgkin Lymphoma aer failure of autologous hematopoietic cell transplan-
tation: Extendedn Follow-up of multicohort Single-Arm Phase II Checkmate
205Trial J Clin Oncol 2018; 36:1428
Disclosure Statement: no disclosure
769
Acquired Hemophagocytic Lymphohistiocytosis as
Paraneoplastic Syndrome in Lymphoma (LA-HLH): atypical
Presentation of Rare Lymphoma Subtypes Requires an
Aggressive Diagnostic Approach
Sebastian Birndt 1; Thomas Schenk 1; Stefani Parmentier 2;
Markus Schaich 2; Stefan Beckert 3; Harald Reiser 3; Jörg Kalla 4;
Andreas Rosenwald 5; German Ott 6; Jochen Talazko 7; Martin Henkes 8;
Andreas Hochhaus 1; Paul Graf La Rosée 8
1Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Deutschland
2Hämatologie, Onkologie und Palliativmedizin, Rems-Murr-Kliniken,
Winnenden, Deutschland
3Klinik für Allgemein- und Viszeralchirurgie, Schwarzwald-Baar-Klinikum,
Villingen-Schwenningen, Deutschland
4Institut für Pathologie, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen,
Deutschland
5Institut für Pathologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
6Abteilung für Pathologie, Robert-Bosch-Krankenhaus, Stuttgart, Deutschland
7Institut für Radiologie und Nuklearmedizin, Schwarzwald-Baar-Klinikum,
Villingen-Schwenningen, Deutschland
8Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-
Schwenningen, Deutschland
Purpose: Acquired hemophagocytic lymphohistiocytosis (HLH) can be
the initial paraneoplastic syndrome at lymphoma onset. Hyperferritine-
mic fever, cytopenia and splenomegaly are diagnostic hallmarks.
Methods: ree patients registered in www.hlh-registry.org with LA-
HLH requiring emergency diagnostic splenectomy are presented.
Results: 1) A 56 y/o patient with relapsing pneumo-pleuritis without specif-
ic histopathologic features developed full blown HLH. PET-CT showed no
accessible hypermetabolic mass. Respiratory failure requiring ICU-treat-
ment triggered etoposide application leading to clinical stabilization. Diag-
nostic splenectomy was performed revealing T-cell rich diuse large B-cell
lymphoma (DLBCL). e patient was cured by 6 x CHOEP and auto-PBSCT.
2) A 53 y/o male organ transplant patient presented with HLH. PET-CT
indicated dim splenic hypermetabolism. HLH-directed treatment sta-
bilized the patient to allow diagnostic splenectomy. Splenic T-cell lym-
phoma was found and T-NHL-directed CHOEP treatment was initiated.
Follow-up will be presented. 3) A 32 y/o male patient presented with
worsening hyperferritinemic fever, neutropenia, splenomegaly, hypo-
brinogenemia, bone marrow phagocytosis. Abdominal probe excision
revealed hemophagocytosis without specic lymphopathology. Due to
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2018
respiratory failure, dexamethasone/etoposide was initiated. Aer stabi-
lization, diagnostic splenectomy was performed revealing T-cell/histio-
cyte-rich DLBCL. e patient was cured with 8 x R-CHOEP and high
dose chemotherapy with auto-PBSCT.
Conclusions: Rare lymphoma phenotypes, inammatory tissue inltra-
tion and severely compromised patients with multiorgan failure make
lymphoma diagnosis in HLH-patients an extra challenge. To over-
come grim prognosis in LA-HLH, resolute diagnostics on concurrent
HLH-treatment require interdisciplinary coordinated interventions1.
Reference:
1. La Rosée et al., Recommendations for the management of hemophagocytic
lymphohistiocytosis in adults. Blood 2019
Disclosure Statement: e authors declare no COI.
804
Comparative Eectiveness of Triplets ContainIng Bortezomib
(B), Carlzomib (C), Daratumumab (D), or Ixazomib (I) in
Relapsed/Refractory Multiple Myeloma (RRMM) in Routine
Care in The US
Katja Weisel 1; Faith Davies 2; Robert Rifkin 3; Caitlin Costello 4;
Saad Usmani 4; Rafat Abonour 5; Antonio Palumbo 6; Dorothy Romanus 6;
Roman Hajek 7; Evangelos Terpos 8; Dawn Marie Stull 6; Hui Huang 6;
Xavier Leleu 9; Jesus Berdeja 10; Hans Lee 11; Michael Thompson 12;
Mario Boccadoro 13; Jerey Zonder 14; Gordon Cook 15; Noemi Puig 16;
Jorge Vela-Ojeda 17; Tomas Skacel 6; Eileen Farrelly 18; Aditya Raju 18;
Ajai Chari 19
1University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
2University of Arkansas for Medical Sciences, Little Rock, United States
3Rocky Mountain Cancer Centers, Denver, United States
4Carolinas Healthcare System,, Charlotte, United States
5Indiana University, Indianapolis, United States
6 Millennium Pharmaceuticals, Takeda Pharmaceutical Company, Cambridge,
United States
7University Hospital Ostrava, Ostrava, Tschechien
8University of Athens School of Medicine, Athens, Griechenland
9CHU la Miletrie, Poiters, Frankreich
10Tennessee Oncology, Sarah Cannon Research Institute, Nashville,
United States
11MD Anderson Cancer Center, University of Texas, Houston, United States
12Aurora Cancer Center, Milwaukee, United States
13Azienda Ospedaliera Citta della Salute e della Scienza, Torino, Italien
14Karmanos Cancer Institute, Detroit, United States
15Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
16Salamanca University Hospital, Salamanca, Spanien
17Hospital de Especialidades Centro Medico Nacional la Raza, Mexico City,
Mexico
18Xcenda, Palm Harbor, United States
19Icahn School of Medicine at Mount Sinai, New York, United States
Purpose: Lack of head-to-head trials of novel agents vs bortezomib-based
triplet regimens (TpRs) renders treatment choice for RRMM dicult,
highlighting a need for real-world (RW) evidence. We conducted a RW
comparative eectiveness analysis of bortezomib (B), carlzomib (C), da-
ratumumab (D), and ixazomib (I) based TpRs in RRMM.
Methods: Patients (pts) with ≥1 prior line of therapy (LOT) initiating a
TpR on/aer 1/1/2014 were followed retrospectively in Optums de-iden-
tied US electronic health record database (2007-2018), a general pop-
ulation-representative dataset. Duration of therapy (DOT) and time-to-
next-treatment (TTNT) were estimated using Kaplan-Meier methods and
compared using Cox models.
Results: Among 1432 pts with 1902 pt-LOTs in the B/C/D/I groups
(n=746/522/418/216) median age was 70/65/68/69 yrs; pts with CRAB
symptoms: 82/87/82/64%; pts with high risk disease (del 17p and/or
t(4;14) and/or t(14;16) and/or 1q21 gain): 16/26/20/14%; IMID and/or
PI refractory: 38/84/85/65%, respectively. B/C/D/I TpRs consisted of an
alkylator in 36/26/5/5% or an IMID-backbone in 54/70/60/91%, respec-
tively; 81/60/44/64% pts received B/C/D/I TpRs in LOT 2-3. At median
f/u of 16.3/13.3/8.6/10.2 mos in the B/C/D/I groups, unadjusted median
DOTs were: 6.0/6.0/6.2/8.4 mos and TTNTs were: 9.8/6.7/7.2/11.1 mos,
respectively. In LOT 2-3, unadjusted median DOTs in the B/C/I groups
were: 8.4/6.3/8.4 mos and TTNTs were: 10.8/7.8/12.7 mos, respectively;
and not estimable in the D-triplet group. Adjusted risk of next LOTini-
tiation/death were statistically comparable for all groups overall; in LOTs
2-3, a trend toward lower risk of next LOTinitiation/death for I- vs B-trip-
let groups (adjusted HR: 0.77; P=0.09) was noted.
Conclusions: e adjusted risk of starting next LOT/death for C-, D- or
I- vs B-based triplets was not signicantly dierent in LOTs 2+ overall, but
showed a lower trend in LOTs 2-3 for I-based triplets. Limitations include
residual confounding due to unobserved treatment selection biases that
are inherent to any non-randomized, observational study.
834
Acquired Hemophagocytic Lymphohistiocytosis in Cancer
Patients: Initial Presenting Paraneoplastic Syndrome of de
novo Malignancy or Complication of Immunosuppressive
Cancer Treatment?
Heidi Hengstler 1; Manuela Wenzler 1; Birgitta Vogt 1; Jörg Kalla 2;
Andreas Rosenwald 3; Jochen Talazko 4; Stefan Beckert 5; Thomas Schenk 6;
Sebastian Birndt 6; Andreas Hochhaus 6; Martin Henkes 1;
Paul Graf La Rosée 1
1Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-
Schwenningen, Deutschland
2Institut für Pathologie, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen,
Deutschland
3Institut fürPathologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
4Institut für Radiologie und Nuklearmedizin, Schwarzwald-Baar-Klinikum,
Villingen-Schwenningen, Deutschland
5Klinik für Allgemein- und Viszeralchirurgie, Schwarzwald-Baar-Klinikum,
Villingen-Schwenningen, Deutschland
6Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Deutschland
Purpose: Acquired hemophagocytic lymphohistiocytosis (HLH) is a
complicating syndrome in cancer patients. HLH may be a paraneoplastic
syndrome of de novo malignancy or a complication triggered by an in-
fection in an immunocompromised patient. Two case reports illustrating
diverse roots of HLH-origin are presented.
Methods: Case report
Results: 1) A 78 y/o male patient with chronic myelomonocytic leukemia
(CMML-1) was treated with 5-azacytidine over 6 months. Aer RSV-pneu-
monia in January 2019, re-admission 4 weeks later due to aggravated dys-
pnea, renal failure and fever of unknown origin was required. Based on
clinical and laboratory fulllment of 5 out of 8 HLH-2004 criteria, the diag-
nosis of acquired HLH secondary to RSV-pneumonia was conrmed. Com-
bined HLH- and CMML treatment with corticosteroids (dexamethasone)
to suppress the cytokine storm and hydroxycarbamid to control leukemic
proliferation reversed pulmonary and renal failure and allowed discharge.
2) A 53 y/o male double organ transplant patient under long-term im-
munosuppression presented with hyperferritinemic (39.404 ng/ml) fever,
pancytopenia, splenomegaly, coagulopathy, hypertriglyceridemia (536
mg/dl), high sIL2R (4.958 U/ml) and bone marrow hemophagocytosis
fullling HLH diagnostic criteria. Nodal status and viral replication test-
ing were unrevealing. PET-CT indicated dim splenic hypermetabolic ac-
tivity. HLH-directed treatment stabilized the patient to allow diagnostic
splenectomy. Splenic T-cell lymphoma was found and T-NHL-directed
treatment was initiated.
Conclusions: Acquired HLH may indicate hidden malignancy mandating
intense diagnostic studies and interventions to detect malignancy. On the
other hand, cancer patients are at increased risk to develop acquired HLH
aer infectious complications. Individual treatment tailoring adapted to
various trigger conditions are required1.
Reference:
1. La Rosée et al., Recommendations for the management of hemophagocytic
lymphohistiocytosis in adults, Blood 2019
Disclosure Statement: e authors declare no COI.
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2018
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2018
Molecular Pathology
Poster
298
The Expression of Genetic Variants of Cytochrome CYP2C9*2
and CYP2C9*3 and their Association with Increased Risk of
Lung Cancer
Darko Katalinic 1; Ivan Aleric 1; Aleksandar Vcev 1; Stephan Bildat 2;
Lilly Soerensen 3
1Faculty of Dental Medicine and Health and Faculty of Medicine, Josip Juraj
Strossmayer University of Osijek, Department of Clinical Medicine, Department
of Internal Medicine, Osijek, Kroatien
2Herford Clinic, Teaching Hospital of the Ruhr-University Bochum, Department
of Hematology and Medical Oncology, Herford, Deutschland
3Department of Cancer Medicine, Divison of Molecular Cancer, Oslo, Norwegen
Purpose: e cytochrome P450 superfamily metabolic enzymes (P450)
could have a possible role in lung cancer susceptibility. erefore, it is im-
portant to dene the overexpression prole of P450 and to establish their
prognostic signicance in subjects with lung cancer. e aim of this study
was to investigate the possible connection among the risk of lung cancer
and frequency of genetic variants of cytochrome CYP2C9 (CYP2C9*2
and CYP2C9*3).
Methods: e study was performed among 359 patients (69% males and
31% females; mean age of 59.96 ± 18.24 years) with diagnosis of stage IV
small-cell (24.6% of patients) and non-small cell lung cancer (75.4% of
patients) compared to 167 healthy subjects (72% males and 28% females;
mean age of 69.96 ± 11.74 years). e distribution of CYP2C9 genetic
variants CYP2C9*2 and CYP2C9*3 was detected using the quantitative re-
al-time polymerase chain reaction (qRT-PCR) restriction fragment length
polymorphism (RFLP) assay. e study was conducted according to the
Declaration of Helsinki, the protocol was reviewed and approved by the
institutional Ethics committee and all patients provided written informed
consent.
Results: No statistically signicant dierences in the distribution of ge-
netic allelic variants CYP2C9*2 and CYP2C9*3 were found among the
patients with lung cancer compared to healthy subjects (p=0.648). e
CYP2C9*2 and CYP2C9*3 genetic variants were expressed at the similar
frequency in cancer and healthy bronchial tissue.
Conclusions: Our data indicate that there is no statistical signicance be-
tween the occurrence of the frequencies of genetic alleles CYP2C9*2 and
CYP2C9*3 and the increased risk of lung cancer.
References:
1. Pratt VM et al. J Mol Diagn.2019 Sep;21(5):746-755.
2. London SJ et al. Pharmacogenetics.1996 Dec;6(6):527-33.
Disclosure Statement: No conicts of interest to declare.
317
Maldi-IMAGiNG - a Tool for Proteomic Characterization
of Tumor Cells
Franziska Homann 1; Daniela Pelzel 1; Günther Ernst 1; Thomas Krüger 2;
Olaf Kniemeyer 2; Ferdinand von Eggeling 1, 3; Orlando Guntinas-Lichius 1
1Department of Otolaryngology, Jena University Hospital, Jena, Deutschland
2Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll
Institute (HKI), Jena, Deutschland
3Jena Biophotonic and Imaging Laboratory (JBIL), Jena, Deutschland
Purpose: Matrix assisted laser desorption/ionization (MALDI) imaging is
a recently developed molecular imaging method. It simultaneously reveals
the label-free detection of numerous molecules in-vitro. In this study, the
method is used in an exemplary way to obtain molecular characteriza-
tion of oropharyngeal cancer tissue and ne-needle aspiration cytology
(FNAC).
Methods: From 20 patients with SCC located in the oropharynx, both
FNAC and tissue samples from the primary tumor zone as well as from
the adjacent normal tissue zones were used. Tissue sections and cell as-
pirates were placed on glass slides. Aer sample specic processing the
sections and the cells were analyzed with MALDI imaging. Aerwards
the MALDI data were compared with histological and cytological stain-
ing. Identication of potential tumor marker was carried out with liquid
chromatography-mass spectrometry (LC-MS/MS).
Results: e assessment of the MALDI data of the tissues resulted in pro-
teomic signatures specic to SCC allowing a clear dierentiation between
malign and benign tissue areas. Dierent, already established as well as
new potential marker proteins could identied. e transfer of these data
onto the aspirates leads to new approaches in the diagnostic of FNAC.
Conclusions: MALDI imaging is an appropriate tool for the comprehen-
sive molecular characterization of tumor tissue and tumor cells of the
head and neck area. e signatures can contribute to improved diagnos-
tics of oropharyngeal carcinoma. In combination with further examina-
tions, they can provide valuable information regarding the inhomoge-
neous therapy response and contribute to a better understanding of the
tumor biology.
Reference:
1. Homann, F. et al. Laryngo-Rhino-Otol 2019; 98(S 02): S72; DOI: 10.1055/s-
0039-1686001.
Disclosure Statement: Franziska Homann has no relevant nancial or nonnan-
cial relationships to disclose.
731
Encyclopedic Tumor Analysis Guided Personalized
Treatments: a Paradigm Shift in Clinical Management
of Advanced Refractory Cancers
Dadasaheb Akolkar 1; Vineet Datta 1; Darshana Patil 1; Ajay Srinivasan 1;
Stefan Schuster 2; Rajan Datar 1
1Datar Cancer Genetics Limited, Nashik, India
2Datar Cancer Genetics Europe GmbH, Eckersdorf, Deutschland
Purpose: Standard of Care therapies have limited ecacy in advanced
refractory solid organ malignancies. Also benets from Checkpoint In-
hibitors are restricted to populations with qualifying molecular features.
We assumed that molecular and cellular investigations (‘Encyclopedic Tu-
mor Analysis, ETA) can reveal unexplored features and target them using
combinations of cytotoxic, targeted and endocrine agents. We report the
results of the pan-cancer RESILIENT trial, where patients with advanced
refractory malignancies received ETA-guided treatments.
Methods: Fresh tumor tissue was obtained from 200 patients and used for
ETA, which included molecular proling (MP: gene alterations/expres-
sion), immunohistochemistry (IHC), and in vitro chemoresistance and
response (CRR) proling against approved anti-tumor agents. MP, IHC
and CRR datasets were integrated to generate patient specic drug priori-
ty lists with projected ecacy and safety. Patients received individualized
combinations, and treatment response was evaluated by FDG PET-CT to
determine Objective Response Rate (ORR), Disease Control Rate (DCR)
and Progression Free Survival (PFS).
Results: Among the 143 patients who received ETA-guided treatments,
126 were evaluable for response per protocol. PR was observed in 54 pa-
tients (ORR = 42.9%) and 114 patients continued to exhibit PR or SD at
study termination (DCR = 90.5%). Median PFS was 134 days. Median
PFS rate at 90 day was 93.9%. No signicant therapy related adverse events
were observed. Most patients reported stable to improved Quality of Life.
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Conclusions: Eta-guided treatments oered meaningful pan-cancer Orr
and Pfs benets in this heavily pretreated population and thus outper-
formed other systemic treatment options incl. Checkpoint Inhibitors.
735
Characterisation of Clonal and Subclonal Allelic Imbalance at
The Hla Locus in a 31 Patient Multi-Region Proled Primary /
Metastasis Clear Cell Renal Cell Carcinoma Cohort
Faiz Jabbar
Francis Crick Institute, London, United Kingdom
Purpose: Metastasis is the primary cause of death in cancer. Large-scale
studies of metastatic disease have not included analysis of matched pri-
mary tumours, which are required to distinguish tumour clones with and
without metastatic potential. Although the treatment of primary tumours
has become more successful, 5 year survival rates for metastatic renal can-
cer remain at 8%. An improved understanding of the genetic dierences
between primary and metastatic tumours could reveal distinct therapeu-
tic vulnerabilities between local and metastatic disease, which if exploited
could improve treatment or prevent metastasis. Immune evasion is re-
quired for tumour progression and metastasis.
We investigated whether genomic alterations causing the loss of human
leukocyte antigen (HLA) alleles would facilitate immune evasion and sub-
sequently promote proliferation and metastasis.
Methods and Results: We acquired the ability to decipher potential
modes of metastatic progression through simultaneous analysis of 418
primary and 278 metastatic biopsies from 31 renal cell carcinoma pa-
tients. Multiple regions from each tumour were biopsied giving us clonal
resolution. AI was investigated using uorescently labelled STR oligonu-
cleotides that were polymorphic within the HLA locus. We showed AIH-
LA was signicantly selected for within the metastases. e detection of
genomic alterations in tumour biopsies is confounded by inltration from
stromal DNA. erefore, we developed a novel bioinformatics tool that
puried and Characterised Allelic Imbalance in Tumours (CAIT). is
was achieved through mathematical deduction of signals originating from
stromal DNA. CAIT increased AIHLA detection, providing insights on
AIHLAs prevalence and timing.
Conclusions: ese results suggest AIHLA could promote metastatic
progression. e characterisation of AIHLA could increase our under-
standing of drug-resistance mechanisms and inform the development of
immunotherapeutic agents targeting neoantigens.
Novel Agents/Early Clinical Trials
Poster
586
Entrectinib in Neurotropic Tropomyosin Receptor Kinase
Fusion Positive (NTRK-FP) Gastrointestinal (GI) Cancers:
Integrated Analysis of Patients (PTS) Enrolled in Three Trials
(STARTRK-2, STARTRK-1, and ALKA-372-001)
Gunnar Folprecht 1; Salvatore Siena 2, 3; George Demetri 4; Robert Doebele 5;
Young Kwang Chae 6; Paul Conkling 7; Ignacio Garrido-Laguna 8;
Pilar Garrido 9; Christian Rolfo 10; Darren Sigal 11; Xinhui Huang 12;
Brian Simmons 12; Chenglin Ye 12; Fortunato Ciardiello 13
1University Hospital Carl Gustav Carus, University Cancer Center UCC/NCT,
Medical Dept I, Dresden, Deutschland
2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan,
Italien
3Università degli Studi di Milano, Department of Oncology and Hemato-
Oncology, Milan, Italien
4Dana-Farber Cancer Institute, Boston, MA, United States
5University of Colorado, Aurora, CO, United States
6Northwestern University, Chicago, IL, United States
7US Oncology Research, Virginia Oncology Associates, Norfolk, VA, United States
8University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, United States
9Ramón y Cajal University Hospital, Madrid, Spanien
10Maryland University, Greenebaum Comprehensive Cancer Center, Baltimore,
MD, United States
11Scripps Clinic, La Jolla, CA, United States
12Genentech, Inc., South San Francisco, CA, United States
13Università della Campania L. Vanvitelli, Dipartimento di Medicina di Precisione,
Napoli, Italien
Purpose: NTRK1/2/3 gene fusions cause expression of chimeric TRK
proteins with constitutively activated kinase activity, leading to oncogenic
potential across several histopathologies. Entrectinib is a CNS-active, po-
tent TRKA/B/C and ROS1 inhibitor. We present integrated ecacy and
safety data from phase 1/2 trials for entrectinib in NTRK-fp solid tumors,
focusing on pts with GI cancers.
Methods: Pts with locally advanced/metastatic NTRK-fp solid tumors
(± baseline CNS disease) conrmed by nucleic acid-based methods
were enrolled in global (>150 sites, 15 countries) trials (ALKA-372-001
[EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2
[NCT02568267]). Tumor assessments were by blinded independent cen-
tral review (BICR) using RECIST v1.1. Primary endpoints (BICR): ob-
jective response rate (ORR), duration of response (DOR). Key secondary
endpoints: progression-free survival (PFS), overall survival (OS), safety.
Results: In the total ecacy-evaluable NTRK-fp population (n=54; 10 tu-
mor types), ORR (BICR) was 57.4% (95% CI 43.2–70.8), with 4 complete
responses (7.4%). Responses occurred in all tumor types. Median (95%
CI) DOR, PFS, OS were 10.4 (7.1–NR), 11.2 (8.0–14.9), 20.9 (14.9–NR)
months, respectively. In the cohort of 8 pts with NTRK-fp GI cancers, re-
sponses by BICR were observed in 1/4 colorectal, 2/3 pancreatic, and 1/1
cholangiocarcinoma pts; all were partial. Investigator-assessed respons-
es in this GI cohort were seen in 2 colorectal and 1 pancreatic pt, and 1
cholangiocarcinoma pt. In the safety population (n=68 pts with NTRK-fp
solid tumors who received ≥1 entrectinib dose), 47% had grade 1/2 treat-
ment-related AEs (TRAEs), 38% had grade 3, 4% had grade 4; there were
no grade 5 TRAEs. TRAEs led to dose reductions in 39.7%, interruptions
in 30.9%, and discontinuations in 4.4% of pts.
Conclusions: Entrectinib was well tolerated and induced clinically mean-
ingful, durable responses in pts with NTRK-fp solid tumors, including pts
with a variety of dierent GI cancers.
Conicts of Interest:
Gunnar Folprecht: Honoraria (self) from Merck, Roche, Sano-Aventis, Bayer,
Mundipharma, Bms, MSD, Servier; Advisory/Consultancy for Merck, Roche,
Sano-Aventis, Bayer, Mundipharma, BMS, MSD, Servier; Research grant /
Funding (institution) from Merck.
Salvatore Siena: Advisory board member for Amgen, Bayer, BMS, CheckmAb,
Celgene, Clovis Oncology, DaiichiSankyo, Incyte, Merck, Novartis, Roche-Genen-
tech, and Seattle Genetics.
George Demetri: Grants, personal fees, non-nancial support, and travel support
for consulting meetings from Novartis, Bayer, Roche, Epizyme and Daiichi-San-
kyo; Grants, personal fees, and travel support for consulting meetings from Pzer;
Personal fees and travel support for consulting meetings from EMD-Serono;
Personal fees from Sano; Grants and personal fees from Ignyta; Grants, personal
fees, and travel support for consulting meetings from Loxo Oncology; Grants,
personal fees, and non-nancial support from AbbVie; Personal fees and travel
support for consulting meetings from Mirati erapeutics; Personal fees and
travel support for consulting meetings from WIRB Copernicus Group; Personal
fees from ZioPharm; Personal fees from Polaris Pharmaceuticals; Personal fees
and travel support for consulting meetings from M.J. Hennessy/OncLive; Grants,
personal fees, and travel support for consulting meetings from Adaptimmune;
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Grants from GlaxoSmithKline; Personal fees, minor equity, and travel support
to Board meetings from Blueprint Medicines, where he serves as a member of
the Board of Directors; Personal fees and minor equity options from Merrimack
Pharmaceuticals, where he serves as a member of the Board of Directors; Personal
fees and minor equity from G1 erapeutics; Personal fees, minor equity options,
and travel support to consulting meetings from Caris Life Sciences; Minor equity
options from Bessor Pharma; Minor equity options from Erasca Pharmaceuticals;
Personal fees and travel support to consulting meetings from Champions Oncol-
ogy; Grants and personal fees from Janssen; Grants, personal fees, travel support
for consulting meetings and non-nancial support from PharmaMar; Use of patent
on imatinib for GIST, licensed to Novartis with royalties paid to the Dana-Farber
Cancer Institute.
Robert Doebele: Honoraria from Genentech/Roche, Takeda/Millenium; Advi-
sory board for Genentech/Roche, Rain erapeutics; Travel reimbursement for
Genentech/Roche, Ignyta; Licensing fees for biological materials from Genentech/
Roche, Ignyta, Foundation Medicine, Loxo Oncology; Consulting for Ignyta, Loxo
Oncology, Bayer, Rain erapeutics; Sponsored research from Ignyta, Loxo Oncol-
ogy; Stock ownership at Rain erapeutics; Licensing fees from patent from Rain
erapeutics and Abbott Molecular.
Young Kwang Chae: Research grants from AbbVie, BMS, Biodesix, Lexent Bio,
and Freenome; Honoraria from Roche/Genentech, AstraZeneca, Foundation
Medicine, Counsyl, NeoGenomics, Guardant Health, Boehringer Ingelheim,
Biodesix, ImmuneOncia, Lilly Oncology, Merck, and Takeda.
Paul Conkling: Research funding from Roche, BMS, and US Oncology Research.
Ignacio Garrido-Laguna: Ad-hoc scientic advisory boards for Array, Ignyta,
Glycyx; Financial support to the Huntsman Cancer Institute from Agios, Bayer,
BMS, Eli Lilly, Halozyme, Incyte, MedImmune, Novartis, OncoMed, Pzer, Taiho
Pharmaceutical, RedHill Biopharma, Glenmark, GSK, NewLink Genetics, ARMO
Biosciences, Amgen, and Rafael Pharmaceuticals.
Pilar Garrido: Consulting and advisory services (self) from Roche, MSD, BMS,
Boehringer Ingelheim, Pzer, AbbVie, Guardant Health, Novartis, Eli Lilly,
AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaking, pub-
lic presentations (self) from Takeda, AstraZeneca, Roche, MSD, BMS, Pzer,
Novartis, Boehringer Ingelheim, Gilead, Rovi; Financial support for clinical trials
(institution) from Roche, MSD, BMS, Takeda, Lilly, Pzer, Novartis, Pharmamar,
Celgene, Sano, GSK, eradex Oncology, Blueprint Medicines; Financial support
for contracted research (institution) from Guardant Health and Sysmex.
Christian Rolfo: Speaker fees from MSD and GuardantHealth; Scientic advisor
for Mylan; Institutional research collaboration with Biomark, Inc.; Non-remuner-
ated collaboration with OncoDNA; Steering scientic committee for Oncopass.
Darren Sigal: Speakers Bureau for Celgene, Bayer; Scientic Advisory Board for
Celularity, Molecular Stethoscope, CureMatch; Patent on using TRK inhibitors to
treat neuroendocrine tumor.
Xinhui Huang: Employment at Genentech, Inc.; Stock ownership at Roche.
Brian Simmons: Employment at Genentech, Inc.; Stock ownership at Roche.
Chenglin Ye: Employment at Genentech, Inc.; Stock ownership at Roche.
Fortunato Ciardiello: Honoraria or consultation fees for speaker, consultancy or
advisory roles from Amgen, Bayer, Bristol-Myers Squibb, Celgene, Merck Serono,
Pzer, Pierre Fabre, Roche, Servier; Direct research funding as the principal inves-
tigator for institutional research projects from
Amgen, Bayer, Merck KGaA, Pierre Fabre, Roche, Ipsen; Institutional nancial
interests, nancial support for clinical trials or contracted research from Merck
KGaA, Roche, Symphogen, Array, Servier, AstraZeneca, and MSD.
All authors: Medical writing and editorial support for the original abstract was
provided by Gardiner-Caldwell Communications, Asheld Healthcare Commu-
nications and sponsored by Roche in accordance with Good Publication Practice
guidelines. Support for third-party editing assistance for this abstract, furnished
by John Carron, PhD, Sammi Cham, BA, and Niamh Gould, BA, of Health Interac-
tions, was provided by Roche Pharma AG. is study was funded by F. Homann
La-Roche, Basel, Switzerland.
766
Identication of Novel HDAC-Inhibitors Targeting Epigenetic
Dysregulations in MDAMB231 Cell Dierentiation
Knud Esser 1; Andrea Kulik 1; Dieter Niederacher 1; Hans Neubauer 1;
Thomas Kurz 2; Tanja Fehm 1
1Heinrich-Heine-University of Düsseldorf, Department of Obstetrics and
Gynecology, Düsseldorf, Deutschland
2Heinrich-Heine-Universität Düsseldorf, Institute of Pharmaceutical and
Medicinal Chemistry, Düsseldorf, Deutschland
Purpose: Targeting tumor specic epigenetic deregulations by activat-
ing silenced cellular dierentiation programs is a promising strategy for
tumor treatment. Epigenetic-acting agents are supposed to potently re-
duce solid cancer cell tumorigenicity and to render cells more prone to
common therapies. Histone deacetylase (HDAC) inhibitors represent one
innovative class of epigenetic drugs known to induce dierentiation in
distinct cancer cells.
Methods: We analysed an in-house library of 20 newly developed
HDAC-inhibitors by a cell-based phenotypic high-throughput screen-
ing system which allows the identication of potential epigenetic-acting
agents via the quantication of two innovative dierentiation markers.
MDA-MB-231 cells were used as in vitro model for complex epigenetic
deregulations leading to an early dierentiation arrest. Dierentiation-in-
ducing potency of the identied compounds was validated by quantifying
the expression of characterized dierentiation markers by qRT-PCR anal-
ysis and compared to clinically relevant HDAC inhibitors.
Results: Testing a databank of 20 novel HDAC inhibitors identied two
compounds as possible hit-candidates. ese compounds showed a high-
er pharmacological ecacy in vitro compared to current clinical HDAC
inhibitors.
Conclusions: We have successfully discovered two new HDAC inhibitors
inducing dierentiation in triple negative MDA-MB-231 cells. Further
studies will be performed to optimize pharmacological potency and to
investigate their potential suitability for anti-tumor drug development.
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2018
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2018
Oncological Pharmacy
Poster
198
Pharmacist in a Multidisciplinary Cancer Care Team in
Germany – Exception or Well-Established Model?
Svenja Dierkes; Annette Freidank; Roland Radziwill
Klinikum Fulda gAG
Purpose: ere is an increasing demand for better management of pa-
tients with cancer due to high numbers of newly diagnosed patients and
the increasing complexity of new chemotherapeutics. Pharmacists are
able to ensure the patient’s safety and quality of life.[1] e objective of this
study is to evaluate the current number of pharmacists embedded in a
multidisciplinary cancer care team in Germany.
Methods: A survey was conducted using a web-based questionnaire. It
addressed all clinical pharmacists in Germany who are ADKA (Federal
Association of German Clinic Pharmacists) members. It was distributed
via ADKA mailing list together with some basic information to ensure
comparability of the answers. It was pointed out that only one response
per hospital pharmacy is allowed.
Results: e ongoing study was started at 8th of August 2019. Up to now
the overall response rate is 34.7% (130 of 375 hospital pharmacies[2]).
Pharmacists are involved in the management of clinical studies (66.9%)
and supportive care (42.3%), as well as in establishing chemothera-
py schemes (66.9%). Although 90.8% of all participants are preparing
ready-to-administer cytostatics, only 15.4% are on ward routinely. Even
less (four pharmacists) are implemented ve days per week for at least
four hours at an oncology ward. Only two (of these four) are involved in
the entire patient care process from admission to discharge counselling
patients ensuring medication safety.
Conclusions: Although the positive impact of a ward pharmacist was re-
ported by some hospitals abroad and clinicians recommend pharmacists
support, the implementation in Germany is still insucient. erefore, we
encourage every clinician to consider a close cooperation with pharma-
cists to improve safe medical treatment.
References:
1. E. M Segal, et al. J Oncol Pharm Pract 2019
2. GBE-Bund.de (Accessed 18th august 2019)
Disclosure Statement: S.D., A.F., and R.R. declare no conict of interest.
567
Medication Safety in Patients Treated with New Oral
Antitumor Agents: A Prospective, Randomized Investigation
on the Impact of Intensied Clinical Pharmaceutical/Clinical
Pharmacological Care on Patient Safety and Well-Being
(AMBORA). Supported by the German Cancer Aid (70112447)
within the Comprehensive Cancer Center Erlangen-EMN
Katja Schlichtig 1; Pauline Dürr 2; Martin F. Fromm 1; Frank Dörje 2
1Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute of Experimental
and Clinical Pharmacology and Toxicology, Erlangen, Deutschland
2University Hospital Erlangen, Pharmacy Department, Erlangen, Deutschland
Purpose: e increasing use of oral anticancer drugs leads to a higher re-
sponsibility for the patient and requires close management to handle Drug
related problems and non-adherence. e main objective of this study is
to investigate the eect of an intensied clinical pharmaceutical/ pharma-
cological care on medication safety and treatment satisfaction in patients
treated with new oral anticancer drugs.
Methods: 200 patients will be randomized to receive either standard
clinical care or intensive care over 12 weeks. A structured clinical phar-
maceutical/pharmacological care program including patient counseling,
medication reconciliation, and side eect management was established.
Primary outcome parameters are the number of drug related problems
(DRP) regarding the oral anticancer drug and patient treatment satisfac-
tion. Further outcome parameters are for example the number of serious
side eects, hospitalization and treatment discontinuation rates.
Results: ese are the results of an interim analysis of 129 patients.
Patients` satisfaction with anticancer treatment is signicantly higher in
the intervention group (TSQM questionnaire 92 vs. 78, p<0.001). e
number of DRP in the control group was higher than in the intervention
group (7.9 vs. 6.8 DRP per patient, n.s.). In particular, serious side eects
were signicantly reduced in the intervention group (1.3 vs. 0.7 side ef-
fects per patient; p<0.05). Rates of hospitalization and discontinuation of
anticancer treatment due to toxicity were higher in the control group (12
vs. 2 hospitalizations; p<0.01, 9 vs. 4 discontinuations; ns).
Conclusions: e data of this interim analysis show that an intensive clin-
ical pharmaceutical /pharmacological counseling can reduce the number
of drug related problems associated with new oral anticancer drugs. e
early intervention reduced serious side eects as well as therapy discon-
tinuation and hospitalization rates due to toxicity. Patients´ satisfaction
was signicantly higher.
Disclosure Statement: e authors have no conicts of interest to disclose.
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2018
Pediatric Cancer
Poster
396
Impairments in Cardiovascular Health and Physical Activity
Early after Treatment for Pediatric Cancer
Sabine Kesting 1, 2; Dominik Gaser 1, 2; Tina Keiser 3; Christiane Peters 2;
Renate Oberhoer 2; Irene von Luettichau 1
1Kinderklinik München Schwabing, TUM School of Medicine, Department
of Pediatrics and Children’s Cancer Research Center, Technical University of
Munich, Munich, Germany
2Institute of Preventive Pediatrics, Department of Sport and Health Sciences,
Technical University of Munich, Munich, Germany
3Department of Sports Medicine and Exercise, Justus-Liebig University Gießen,
Gießen, Germany
Purpose: Cardiovascular diseases in pediatric cancer survivors are known
late sequelae1. Cardiovascular health is usually related to physical activi-
ty (PA). Reduced PA during cancer treatment results in impaired motor
performance2. erefore, reintegration into sports structures might be
aected.
Methods: Participants (6-18 yrs, mixed entities) were recruited during
follow-up care from April to June 2019. Peripheral and central systolic/di-
astolic blood pressure (pSBP/pDBP/cSBP) and pulse wave velocity (PWV)
were assessed using the Mobil-O-Graph®. e MOON test scaled motor
performance. PA aspects were quantied with the KiGGS study question-
naire. All data was compared to reference values.
Results: 40 children (11.3±3.8 yrs, 50% ) were recruited 1.6±1.8 years
post-treatment. PSBP (z-score 0.9±1.7, p = 0.003), pDBP (0.8±1.9,
p = 0.033) as well as cSBP (≥8 yrs: 0.6±1.3, p = 0.011) were signicantly in-
creased compared to reference values. PWV was elevated (<8 yrs: 1.2±2.9,
p = 0.374; ≥8 yrs: 0.6±1.9, p = 0.127). Motor performance was reduced in
nearly all dimensions. 17% reported 60 min of daily PA as recommended
by the WHO. 50% were active sports club members, but 1/3 did not re-
sume their former membership.
Conclusions: Early aer treatment, children show increased blood pres-
sure, a risk factor for cardiovascular diseases. Impaired motor perfor-
mance and low PA underline the support needed regarding engagement
in PA to potentially counteract risk factors and improve cardiovascular
health. Implementation of sports oers during and aer treatment should
be considered as a meaningful, cost-eective preventive approach in
terms of late eects associated with physical inactivity.
References:
1. Hudson M et al. Clinical Ascertainment of Health Outcomes Among Adults
Treated for Childhood Cancer, JAMA 209; 2013:2372-81.
2. Ness KK et al. Limitations on physical performance and daily activities among
long-term survivors of childhood cancer. Am Intern Med 14; 2006:639-47.
502
Short and Long Term Outcome for Patients with Surgical
Removal of Sacrococcygeal Teratoma in Newborns and
Infancy
Maria Ai 1; Vera Schellerer 2; Manuel Besendörfer 2
1Uniklinik Erlangen, Kinderklinik, Erlangen, Deutschland
2Uniklinik Erlangen, Kinderchirurgie, Erlangen, Deutschland
Purpose: is study evaluates the short and long term outcomes of new-
born and infant cases with sacrococcygeal teratoma removal. We exam-
ined the physical and neurological impairment aecting these patients.
Methods: A total of 21 patients underwent surgical procedure between
July 2001 and July 2019 in our pediatric surgery department. We gathered
information from the patient medical records, postoperative medical in-
terviews, and performed physical examinations. We used this information
to evaluate the status and the extent of the impairment of the patients. e
patients received follow up treatment in according to the MAKEI recom-
mendations for duration of 10 years.
Results: 21 patients had surgical procedure through our department due
to sacrococcygeal teratoma (male: n = 5, female n = 16). SCT are more
common in females with a 3 to 4:1 ratio. Pre-operative assessment in-
cluded prenatal ultrasound (n = 20), prenatal MRI (n = 7), neonatal MRI
(n = 10). e distribution of our Altman classication was: 14% Altman I
(n = 3), 57% Altman II (n = 12), 10% Altman III (n = 2), 10% Altman IV
(n = 2), 10% Altman unknown (n = 2). e surgery was performed at the
age of diagnosis which was on average the 3nd day of life (range: 0 to 13
day of life). e weight median was by 2800g with a range of 2570 g. Out
of the 21 patients, 12 tumors were completely removed with R0 surgical
resection (n = 12), 3 tumors with R1 (n = 3) and 6 tumors with RX (n = 6)
surgical resections. Histological ndings included predominantly chon-
droid (n = 12) and neuroectodermal (n = 10) parts. e maturity level
was evaluated: 33% GC 0 (n = 7), 24% GC 1 (n = 5), 14% GC 2 (n = 3),
5% GC 3 (n = 1), 14% GC unknown (n = 6). Post-operative complications
included surgical site infections (n = 6), bowel perforation (n = 1), and
post-operative mortality (n = 2).
Conclusions: Sacrococcygeal teratoma is a heterogeneous entity of the
germline tumors and the prognosis is signicantly better for patients who
had R0 surgical resection and low GC scores. Postoperative and long term
complications are tolerable. Follow ups are necessary to determine future
reoccurrence of the tumor.
625
A Comprehensive Map of Genetic Vulnerabilities in ATRT
Subgroups
Daniel Merk 1; Sophie Hirsch 1; Cristiana Roggia 2; Federica Piccioni 3;
Michael Spohn 4, 5; Ulrich Schüller 5, 6; Ghazaleh Tabatabai 1
1Interdisciplinary Division of Neuro-Oncology, Departments of Neurology
& Stroke and Neurosurgery, Laboratory of Clinical and Experimental Neuro-
Oncology, Hertie-Institute for Clinical Brain Research, University Hospital
Tübingen, Eberhard Karls University Tübingen, Tübingen, Deutschland
2Institute of Medical Genetics and Applied Genomics, University Hospital of
Tübingen, Eberhard Karls University Tübingen, Tübingen, Deutschland
3Broad Institute of MIT and Harvard, Cambridge, United States
4Bioinformatics Core, University Medical Center Hamburg-Eppendorf ,
Hamburg, Hamburg, Deutschland
5Research Institute Children`s Cancer Center Hamburg, Hamburg, Deutschland
6Department of Pediatric Hematology and Oncology, University Medical Center
Hamburg-Eppendorf , Hamburg, Hamburg, Deutschland
Purpose: Brain tumors are the leading cause of cancer-related deaths in
children and adolescents. Embryonal brain tumors are a group of high-
grade neoplasms which primarily aect young patients, and atypical
teratoid rhabdoid tumors (ATRTs) are the second most common type
of tumor within this group. In spite of intensive research eorts and the
knowledge of molecular mechanisms driving subgroup-specic heteroge-
neity within ATRTs, survival estimates stay relatively low as compared to
other tumor entities with a median survival of around 17 months. More
ecacious and durable therapies are urgently needed to improve the sit-
uation of patients.
Methods: We investigated genetic, epigenetic, and transcriptional features
of seven distinct human ATRT cancer cell lines in order to assign those
cell lines to three molecular subgroups described for ATRTs. Subsequent-
ly, we will perform genome-wide CRISPR/Cas9 knockout screens for
these ATRT cell lines in order to identify genetic vulnerabilities and novel
therapeutic targets for this tumor entity.
Results: Detailed analyses including mRNA expression- and DNA meth-
ylation-based prediction approaches provide evidence that our selection
of ATRT cell lines (BT12, BT16, CHLA02, CHLA04, CHLA05, CHLA06,
CHLA266) recapitulates features of all three molecular subgroups of
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ATRT, namely ATRT-TYR, ATRT-SHH, and ATRT-MYC. Dependen-
cies discovered in the rst screen using BT12 cells were highly enriched
for fundamental cellular processes such as transcription and translation,
thereby validating our approach. We identify 190 BT12-specic cell es-
sential genes, including 44 genes in potentially druggable categories and
seven genes representing clinically actionable targets. We are preparing to
screen additional ATRT cell lines of all molecular subgroups in order to
establish a comprehensive overview of ATRT vulnerabilities.
Conclusions: Our data will provide a comprehensive map of dependen-
cies for distinct ATRT subgroups which will serve as a starting point in the
development of targeted therapies for this tumor entity.
682
Feasibility of Indoor-Wall Climbing with Pediatric Cancer
Survivors
Vivien Lösse1, Aram Prokop2, Sarah Otten1, Eva Schmidt1, Benjamin
Kröger1, Volker Maas2, Wilhelm Bloch3, Julia Däggelmann1
1Institut für Kreislauorschung und Sportmedizin Abt. molekulare und zelluläre
Sportmedizin, Deutsche Sporthochschule Köln, Köln, Deutschland,
2Kinderkrankenhaus Amsterdamer Straße, Köln,
3Institut für Kreislauorschung und Sportmedizin, Deutsche Sporthochschule
Köln
Purpose: To assess feasibility of an indoor-wall climbing intervention for
pediatric cancer survivors.
Methods: Eight pediatric cancer survivors (6.50 – 20.67 years, mixed di-
agnoses) (patient group, PG) and ve healthy controls (7.42 – 20.67 years)
(healthy group, HG) participated in an indoor-wall climbing intervention
for 8-9 weeks. Supervised training was oered once a week for 60 min.
Feasibility was assessed by adverse events leading to study drop-out. Addi-
tionally, side eects like temporary muscle pain/ injuries and compliance
were evaluated. An evaluation questionnaire was used to determine train-
ing acceptance by participants and parents.
Results: No adverse events or side eects were documented. Only one
child reported that the climbing intervention was too exhausting due to
insucient breaks. Participants completed an average of 56,78% (25% –
100%) of the oered training sessions. Reasons for non-participation were
reported in 28 cases which were lack of time (80%) and medical issues like
infections (20%). Overall, 13 children (PG and HG) and 9 parents (PG
and HG) completed the questionnaire. Children generally liked the climb-
ing intervention and stated to feel stronger and more condent. ey were
interested in continuing indoor wall-climbing.
Conclusions: Indoor-wall climbing with pediatric cancer survivors is fea-
sible and well-accepted. Study results encourage to assess potential eects
of indoor-wall climbing in pediatric oncology.
Disclosure Statement: e authors declare nothing to disclose.
818
Secondary Malignancies following Ewing Sarcoma Treatment
Isabelle Kaiser
Kinderheilkunde III, Universitätsklinikum Essen
Purpose: Ewing Sarcoma (EwS) is an aggressive, bone- and so tissue
sarcoma found in children, adolescents and young adults. Due to intense
multimodal therapy, survival rates have increased to 75% in patients with
localized disease1. Consequently, long-term surveillance of late eects
has gained importance. We investigated secondary malignant neoplasms
(SMNs) following EwS-treatment. is study investigated relative risk and
prognostic factors of SMN development and compared dierent SMN risk
characteristics. Time of latency between EwS and SMN diagnosis was also
examined.
Methods: e following GPOH studies supplied data: CESS 86, CESS 91P,
EICESS 92 and Euro-Ewing 99; data from a total of 3097 patients were
included. Time to SMN occurrence and survival rates aer EwS diagnosis
were analyzed. Cumulative incidences and Odds ratios for cause-specic
risks were computed.
Results: Median age of EwS diagnosis was 16 years (2–68 years). Notably,
35% had been diagnosed with metastatic EwS. Metastases were localized
mainly in the lung, bone marrow and other bones. A total of 75 patients
(54% female, 46% male) with 76 SMNs were identied. Two patients
developed two dierent SMNs. SMNs manifested as hematological neo-
plasms (42%) and solid tumors (58%) at a mean latency time of 7.8 years
following primary EwS diagnosis. In total, 58/74 (78%) patients received
radiation treatment. Twelve out of 15 (80%) observed Osteosarcomas
were localized within a previously irradiated eld.
Conclusions: Ewing Sarcoma survivors are at risk of developing SMNs. In
particular, hematological neoplasms (AML and MDS), as well as Osteo-
sarcomas were recorded following EwS treatment.
Reference:
1. Grünewald T., Cidre-Aranaz F., Surdez D. et al. (2018). Ewing sarcoma. Nature
Reviews. Disease Primers 4(5). doi: 10.1038/s41572-018-0003-x
Palliative Care
Poster
41
Parental Dealing with Diuse Intrinsic Pontine Glioma in
Children
Kalinka Radlanski 1; Maite Hartwig 2; Uwe Kordes 1
1Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische
Hämatologie und Onkologie, Hamburg, Deutschland
2KinderPaCT - Hamburg e.V., Hamburg, Deutschland
Purpose: Diuse intrinsic pontine glioma (DIPG) in children is a dis-
mal disease with median overall survival (OS) of less than a year. Usually
palliative care is involved. Open communication about death eases dying
for children and surviving for parents. is study establishes case reports
based on parental confrontation with DIPG. During the course of DIPG
designated key points exist. We determine specic needs of parents and
children as well as typical problems in interaction between families and
care givers. e results lead to recommendations and improvements for
existing treatment concepts.
Methods: We conducted a problem-oriented guided interview followed
by a qualitative content analysis according to Mayring.
Results: 13 parents of 7 children (aged 5-16 years) were interviewed. e
childrens median OS was 8 months and 4 days. Palliative home care was
involved in 5 families. Palliative care generally met the needs of the exam-
ined families. Parents stated overall satisfaction and comfort regarding to
most subjects (management of physical symptoms and support, provision
of information, family support, patient psychological care). Communica-
tion about death is a relevant inductive category. Out of 7 children it was
assumingly spoken openly to only one child. Two families remained in
mutual pretense. Two children were actively prevented by their parents
to have open communication. In two other cases the concept remains un-
clear. All parents regret that they have not talked to their children about
death.
Conclusions: Parents are less burdened when palliative care is involved
in the treatment of their childrens DIPG. e overall load of statements
about not talking with children about their death meets the relevance of
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this topic in literature. Concepts need to be established on how to rise
attention to the chances that open communication about death oers for
both children with life-limiting diseases and their families.
Reference:
1. Radlanski K., Hartwig M., Kordes, U. (2019) Parental Dealing With Diuse
Intrinsic Pontine Glioma in Children. EAPC Abstracts, Palliat Med
56
Dealing with Desire to Die in Patients with Incurable Cancer:
Recommendations of the German S3 Guideline Palliative
Medicine
Raymond Voltz 1, 2, 3, 4; Kerstin Kremeike 1; Anne Pralong 1; Steen T Simon 1;
Claudia Bausewein 5; Reinhard Lindner 6
1Departement of Palliative Medicine, University of Cologne, Faculty of Medicine
and University Hospital, Cologne, Deutschland
2Center for Health Services Research (ZVFK), University of Cologne, Faculty of
Medicine and University Hospital, Cologne, Deutschland
3Center for Integrated Oncology (CIO), University of Cologne, Faculty of
Medicine and University Hospital, Cologne, Deutschland
4Center for Clinical Studies (ZKS), University of Cologne, Faculty of Medicine and
University Hospital, Cologne, Deutschland
5Department of Palliative Medicine, Ludwig-Maximilians-University Munich,
Faculty of Medicine and Munich University Hospital, München, Deutschland
6Institute of Social Work, University Kassel, Faculty of Humanities, Kassel,
Deutschland
Purpose: Desire to die (DD) is common in palliative patients. Medical
advance and improved therapy options do not cancel out DD, but on the
contrary many patients think about dying and ask about the meaning of
life. Health practitioners are oen confronted with these thoughts. e
current national and international state of knowledge and experience in
dealing with DD oers orientation and assurance in responding to it in an
appropriate manner.
Methods: Development of evidence and consensus based recommenda-
tions with the participation of more than 60 professional societies.
Medline, PsycInfo, and Cochrane Library databases were systematical-
ly searched for relevant publications on proactively addressing DD, and
selected according to dened inclusion criteria. Findings were assessed
and built the base for developing recommendations. Evidence based and
consensus based statements were consented in a formal process.
Results: e expert panel agreed on 19 statements and recommendations
dealing with DD issues such as dierential diagnosis, potential back-
ground and meaning, how to deal with DD, possible options for action
and legal framework. e handling of DD within the treatment team, pos-
sible support from external experts and the involvement of relatives are
also covered within the guideline.
Conclusions: e guideline aims to support decision-making in practice
and provides systematically developed recommendations on the basis of
the best available evidence and clinical experience of a large number of
experts. e recommendations concerning DD aim at helping with (pro-
actively) addressing potential DD as well as dealing with them. ere-
fore they should be considered a contribution to the advancement of
multi-professional competence in palliative care.
Disclosure Statement: e authors declare no conict of interest.
123
Stability of Cancer Patients´ Unmet Spiritual Needs and
Spiritual Wellbeing in Palliative Care Units
Arndt Büssing 1; Klaus Baumann 2; Jochen Rentschler 3; Gerhild Becker 4
1Professorship Quality of Life, Spirituality and Coping, Witten/Herdecke
University, Herdecke, Deutschland
2Caritas Science and Christian Social Work, Albert-Ludwig University Freiburg,
Freiburg, Deutschland
3Department Hematology / Oncology / Palliative Medicine, Ortenau-Klinikum
Oenburg-Kehl, Oenburg, Deutschland
4Chair of Palliative Medicine, Clinic for Palliative Medicine, Freiburg University
Hospital, Freiburg, Deutschland
Purpose: Duration of patients´ stay in palliative care units (PCU) is de-
creasing, and thus options to profoundly provide spiritual care. Aim was
thus to analyze patients´ unmet spiritual needs at the beginning and end
of their PCU stay.
Methods: Pre-post analysis (paired t-test) of 65 patients´ spiritual needs
(SpNQ-20), spiritual wellbeing (FACIT-Sp), life satisfaction (BMLSS), sat-
isfaction with team support (BMLSS) and perceived health status (VAS)
with standardized questionnaires in two PCUs. IRB-Approval 316/14.
Results: Patients´ primary diagnosis was cancer (99%; 62% women, mean
age was 64±11 years; 73% Christians, 2% Muslims, 24% without religious
aliation). e Meaning component of their spiritual wellbeing scored
highest (3.19±0.70), followed by Peace (2.45±0.78) and Faith (1.80±1.34).
Among unmet spiritual needs, Inner Peace needs (1.59±0.91) and Giv-
ing/Generativity needs (1.42±0.93) scored highest, Religious needs
(0.88±0.93) and Existential needs (0.72±0.83) scored rather low. Most
stayed for 2-3 weeks at the PCU (65%). Within this time frame, neither
spiritual needs nor spiritual wellbeing nor life satisfaction changed sig-
nicantly, while their perceived health status improved (M -8.7±18.6;
p<.001). Within the sample, 66% felt that their spiritual needs were sup-
ported ’very well’ by the hospital sta (which is not specically trained in
spiritual care issues), 21% stated ‘quite well, and 13% were not satised.
Conclusions: e time frame to provide profound spiritual care support
is rather limited. Although most felt supported in terms of their spiritual
needs, neither their needs nor their wellbeing scores changed signicantly.
Nevertheless, the individual development of spiritual needs and spiritual
wellbeing might be very dierent, and thus hospital sta has to be aware
that also an ‘aggravation’ of unmet needs could be expected (indicating
either stronger awareness or increase of fear and burden).
Disclosure Statement: e authors disclose any conicts of interest.
143
Development of a Training Program to Enhance
Communication Skills Regarding Early Referral to Palliative
Care in Advanced Cancer Patients – The Palli-Kom Study
Nele Harnischfeger 1; Hilke M. Rath 2; Anne Letsch 3; Peter Thuss-Patience 4;
Bernd Alt-Epping 5; Carsten Bokemeyer 1; Corinna Bergelt 2; Karin Oechsle 1
1Palliativmedizin, 2. Medizinische Klinik und Poliklinik, Universitätsklinikum
Hamburg-Eppendorf, Hamburg, Deutschland
2Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum
Hamburg-Eppendorf, Hamburg, Deutschland
3Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und
Tumorimmunologie, Charité-Universitätsmedizin Berlin, Campus Benjamin
Franklin, Berlin, Deutschland
4Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und
Tumorimmunologie, Charité-Universitätsmedizin Berlin, Campus Virchow,
Berlin, Deutschland
5Klinik für Palliativmedizin, Universitätsmedizin Göttingen, Göttingen,
Deutschland
Purpose: To develop a communication training for physicians who treat
cancer patients to promote an early referral to palliative care in advanced
cancer patients. e training aims to strengthen the ability to address pal-
liative care related topics constructively and early during disease trajecto-
ry. e basis of the training development will be focus groups, literature
and expert discussions.
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Methods: In addition to an intensive literature search to identify relevant
training contents, we conducted four focus groups with a total of 28 physi-
cians of varied specialization and levels of experience (M age = 39.5, SD =
8.92). Discussed topics were professional and communicative competen-
cies, personal barriers and the desired training structure. e talks were
audiotaped, transcribed and analyzed via qualitative content analysis.
Results: Due to the focus groups (average length: 90 minutes) we identi-
ed numerous aspects, which the participating physicians considered to
be crucial to the training. e need for a rectication of the understanding
of palliative care including its benets was especially emphasized. Also,
knowledge about symptom control and palliative care structures seem of
particular importance. Highlighted communication skills were an adapt-
ed language, the balance between honesty and hope, and the consider-
ation of individual information needs. Crucial personal barriers are a high
emotional involvement, especially in young patients, and the diculty of
being unable to heal. Participants desire a realistic training with a high
practical part. Personal aspects like coping shall be addressed.
Conclusions: e daily experience of physicians is a valuable source to
identify necessary competencies for early integration. Physicians have
precise expectations towards a training on communicating palliative care
related topics. Results of the focus groups were supplemented by ndings
from literature search. is will now be used to specify content and didac-
tics of the training.
Disclosure Statement: e authors declare no conict of interest.
296
Full Local Control in a Giant Ulcer of Advanced Breast Cancer
by Denitive Radiotherapy Only
Kalinka Radlanski; Dipl.-Phys. Oliver Bislich; Björn Peters;
Fabian Fehlauer
Strahlenzentrum Hamburg MVZ, Hamburg, Deutschland
Purpose:Female patient, *1931 with satisfying health conditions, Kar-
nofsky index (KI) 70%. Patient is widowed with no children and lives
in her own home with the support of a local care team. She was acutely
hospitalized with delirium due to exsiccosis and a suspected mild stroke.
Accidentally a large high risk tumor of the le mamma was found (cT4
cN0 cM0, triple negative hormone receptor status, Ki67 index 90%). In-
terdisciplinary oncologic tumor conference advised surgery followed by
chemotherapy. Both declined by patient, she primarily consulted radio-
therapy. Clinical examination showed a giant ulcer of 10 x 12 x 8 cm in
upper quadrants of le breast with spontaneous bleeding, brinous slimy
coat/secretion and strong odour. Patients only distress was caused by ul-
ceral staining of her clothes.
Methods:Ambulatory radiotherapy (RT) of le mamma with 48 Gray
(Gy) photons in 3 Gy single fractions, ve days a week with the use of a 8
mm moulage. Wound care with Octenilin® and manual necrosis ablation.
Weekly doctor’s visits.
Results:36,0 Gy: bleeding has stopped, yellowish brinous coat. 48,0 Gy:
much more compact ndings, no spontaneous bleeding/secretion. Mod-
est erythema of treated mamma (common toxicity criteria, CTC=2), two
small epitheliolyses (CTC=0-1), no edema of mamma or arm. KI 70%.
Very satised patient. Wound care is to be continued. 1. follow-up, 3
months aer RT: mild erythema, signicantly smaller tumor. Ulcer almost
healed, 5 cm residuum with slimy coat. Mild edema of treated mamma.
Very satised patient, KI 90-100%. 2. follow-up, 7 months aer RT: intact
skin, former ulcer is fully healed. No edema. Very satised patient, KI
90-100%.
Conclusions: Denitive RT as sole treatment can be considered as a su-
cient palliative strategy to achieve local control in advanced breast cancer
with ulceration. We controlled local symptoms and reached full healing of
the ulcer. We were able to not only sustain but raise the quality of life of
a self-sucient senior in the severe health condition of advanced breast
cancer. She experiences no impairment of daily life.
333
Music at the Palliative Care Unit (PCU) – A Volunteer Project
with Young Adults
Katrin Berndt 1; Daniela Heise 1; Heike Büntzel 2; Jens Büntzel 2
1Schwimmverein Nordhausen, Nordhausen, Deutschland
2Abteilung Palliativmedizin, Südharz-Klinikum Nordhausen, Nordhausen,
Deutschland
Purpose: Music could help to vercome social isolation at palliative care
institutions. Young volunteers have combined swim sports with this social
idea.
Methods: Since 2006 the Swim Club Nordhausen 1990 is taking part in
24-h-competitions in order to fundraise the project of our PCU. e club
donated an e-piano in 2014 and from then every 2-3 month concerts
were given to our patients. Each concert has 20-30 visitors and patients
listening the young artists. In 2018 we were able to engage a professinal
guitarrist making active music together with the individual patients every
month.
Results: 167 young volunteers have taken part in the fundraising project.
26 concerts were organized presenting piano, guitar or choral music since
March 2014. 289 patients were able to take part in these concerts. More
than 600 family members were guests of the young artists. Active music
oer was used by 53 patients at 11 sessions, e.g. 40% of possible patients
have had benet from this new apporach since January 2018.
Conclusions: Palliatve patients consume music in passive as well as active
way. Its integration helps to overcome their isolation. Furthermore young
artists become embassadors of hospice ideas.
Disclosure Statement: e authors disclose any conict of interest.
574
“But you need a Questionnaire Like This”: Real Life Experience
of Quality of Life Assessment in Outpatients with Lung and
Prostate Cancers – A Longitudinal Cohort Study
Eileen Ratzel 1; Christina Gerlach 1, 2; Ina Pretzell 2; Elke Tafel-Stein 3;
Thomas Kindler 2; Martin Weber 1
1Interdisziplinäre Abteilung für Palliativmedizin, Universitätsmedizin Mainz,
Mainz, Deutschland
2Universitäres Centrum für Tumorerkrankungen, Universitätsmedizin der
Johannes Gutenberg Universität Mainz, Mainz, Deutschland
3Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsmedizin der
Johannes Gutenberg Universität Mainz, Mainz, Deutschland
Purpose: Quality of life (QoL) assessment with patient-reported outcome
measurements (PROMs) improves patients’ QoL. It is a prerequisite in the
certication process for oncology centers of the German Cancer Society
(DKG). e aim of the study was to test the feasibility of PROMs (Inte-
grated Palliative Outcome Scale IPOS, and Distress ermometer DT) in
outpatients with advanced lung and castration-resistant prostate cancer,
both diseases beyond recovery.
Methods: e process of longitudinal QoL assessment with IPOS and
NCCN-DT was observed for 15 months. Besides patients’ distress we also
analyzed the numbers of requests for supportive services as a consequence
of the patients’ ndings in the questionnaires. Focus group interviews
with patients, informal caregivers and health care professionals (HCP)
were thematically analyzed.
Results: Ninety-seven percent (n=125) out of 129 eligible patients
received a questionnaire for one time at least. However, quarterly
assessment as recommended was achieved only in 60% of prostate
cancers, and 48% of lung cancer patients. IPOS showed a high face and
content validity and both questionnaires were well accepted. Patients did
not feel uncomfortable with lling in the questionnaires. HCP found the
instruments helped to focus and structure the time for the doctor-patient-
contact. Some patients pointed out diculties with the DT in terms of
comprehension. Due to lacking process and to organizational challenges
the achieved response rates were low as were the rates of consultations
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with supportive services. Monitored hand-over of the questionnaires
improved their implementation.
Conclusions: PROMs were regarded as important by lung and prostate
cancer outpatients as well as HCP. To facilitate consequences they should
be realized as standardized intervention rather than pure assessment. e
results must be accessible in a straightforward way to gain the maximum
benet for patients and health care processes. e eects on a direct data
input into the electronic patient chart, such as results from laboratory
tests, should be tested.
Pege
Poster
34
Anwendung des Niedrigenergielaser (Low Level Laser LLL)
Zur Prävention und Behandlung der oralen Mukositis bei
onkologisch erkrankten Erwachsenen und Überprüfung der
Wirksamkeit – Eine prospektive Beobachtungsstudie
Rudolf Nieth
Marburg, Universitätsklinikum UKGM, Marburg, Deutschland
Zweck: Orale Mukositis (OM) ist eine der Nebenwirkungen der Trans-
plantation hämatopoetischer Stammzellen(HSCT), die zu erheblicher
Morbidität führt. Ziel dieser Studie war es, die Wirkung eines speziellen
Mundpegeprogramms mit Lasertherapie bei der Behandlung von Pati-
enten, die eine HSCT erhalten zu überprüfen.
Methoden: Bei den Patienten wurden ab dem Tag der Behandlung ein-
mal täglich beide Wangen vorbeugend von außen für maximal 5:20 Mi-
nuten mit dem Low Level Lasergerät Twin 21+ mit den Einstellungen
21x100mW, 16,0J/LD Multifrequenz bestrahlt
Ergebnisse: Die hier vorgelegte Arbeit zeigt die positive Wirkung des
Lasers für das beschriebene Patientenklientel. Die Schwere der Mukositis
nach WHO konnten über alle Schweregrade hinweg reduziert werden.
Fazit: Eine Einführung der prophylaktischen Behandlung von onkol-
ogischen Patienten mittels der Lasertherapie kann somit zugestimmt
werden. Auch eine Kostenreduktion ist zu erwarten.
Quellenangaben:
1. Oberoi, S.; et al. (2014): Eect of Prophylactic Low Level Laser erapy on
Oral Mucositis. A Systematic Review and Meta-Analysis. In: PLoS ONE 9 (9),
S. e107418.
2. Blijlevens, et al. (2008): Prospective Oral Mucositis Audit. Oral Mucositis in
Patients Receiving High-Dose Melphalan or BEAM Conditioning Chemo-
therapy--European Blood and Marrow Transplantation Mucositis Advisory
Group. In: Journal of Clinical Oncology 26 (9), S. 1519–1525.
3. Curra, M.; et al. (2018): Chemotherapy protocols and incidence of oral mucosi-
tis. An integrative review. In: Einstein (Sao Paulo, Brazil) 16 (1), eRW4007.
4. Bezinelli, L., et al. (2014): Cost-eectiveness of the introduction of specialized
oral care with laser therapy in hematopoietic stem cell transplantation. In:
Hematological oncology 32 (1), S. 31–39.
5. Lalla, R. V.; et al. (2014): MASCC/ISOO clinical practice guidelines for the
management of mucositis secondary to cancer therapy. In: Cancer 120 (10), S.
1453–1461.
Oenlegungserklärung: Die Fa. MKW Laser hat keinerlei Einuss auf die Ergeb-
nisse oder anderweitig ausgeübt
49
Immuntherapie: Herausforderung für Pegefachkräfte in Der
Thorax-Onkologie
Cornelia Kloft
Lungenkrebszentrum Mittelhessen, Klinik Waldhof Elgershausen, Greifenstein,
Deutschland
Zweck: In der orax-Onkologie, insbesondere beim nichtkleinzelligen
Lungenkarzinom, ndet eine rapide Entwicklung neuer erapien statt.
Diese Entwicklung stellt die onkologische Pege vor immer neue Heraus-
forderungen. Hier ist ein Wissensdezit zu verzeichnen, was die Wirk-
weise und die immunbedingten Nebenwirkungen angeht.
Methoden: Der Aufsatz erklärt die Wirkungsweise der Immunonkol-
ogie und geht auf die immunbedingten Nebenwirkungen ein. Es wird
eingegrenzt, bei welchen Entitäten in der orax-Onkologie diese era-
pieform hauptsächlich zum Einsatz kommt. In einer Reihe von Patienten-
interviews wurde beispielha der Wissensstand von einzelnen Patienten
ermittelt. Viele Informationsmaterialien, die für die Patientenedukation
zur Verfügung stehen, werden im Aufsatz verglichen. Es werden emen
für Beratungsgespräche herausgearbeitet. Um eine gute Beratungskompe-
tenz in der Pege zu gewährleisten, ist die Mitarbeiterschulung ein wich-
tiger Aspekt.
Ergebnisse: Den besten Schutz vor unerwünschten Nebenwirkungen
könnten Krebspatienten haben, wenn sie selbst Experten für ihre Behan-
dlung wären. Der Schwerpunkt in der Patientenedukation sollte daher auf
dem Beratungsgespräch liegen. Wenn Patienten Fragen haben, sind Peg-
ende häug die ersten Ansprechpartner. Deshalb spielen sie eine wichtige
Rolle als Informationsgeber. Um das Wissen der Pegenden zu erweitern,
ist die innerbetriebliche Fortbildung als fester Bestandteil der Mitarbeit-
erschulung unverzichtbar.
Fazit: Eine gelungene Immuntherapie bedeutet für unsere Patienten eine
deutlich längere Überlebenszeit bei relativ guter Lebensqualität. Das Ex-
pertenwissen von Patienten und Pegenden kann dazu einen entschei-
denden Beitrag leisten.
73
Umgang mit dem Fatigue-Syndrom bei Krebspatienten
Heike Hingst; Ute Stutz
Universitätsmedizin Greifswald, Patienteninformationszentrum, Greifswald,
Deutschland
Zweck: Um Aufschluss über die Einstellung zum Erscheinungsbild des
Fatigue-Syndroms zu bekommen und zu sehen, wo noch Informationsbe-
darf besteht, wurde eine Befragung durchgeführt.
Ziel der Befragung war:
den Wissenszustand der ärztlichen und pegenden Kolleg*innen
festzustellen
eine Fatigue-Prophylaxe auch in anderen Bereichen des onkolo-
gischen Zentrums zu etablieren
den Wissensstand zu verbessern und Weiterbildungen gezielt
planen zu können
Methoden: Es wurde in einem Zeitraum von 4 Wochen auf 13 Stationen
erfragt, wie das Wissen über das Fatiguesyndrom selber eingeschätzt wird
und durch welche Symptome Betroene am meisten beeinträchtigt sind.
Weiterhin wurde erfragt, ob auf Zeichen eines Fatigue-Syndroms geachtet
wird und wie der weitere Umgang bei Erkennen von Symptomen erfolgt.
Ergebnisse: Es wurden 322 Bögen ausgeteilt, von denen 115 ausgefüllt
wurden. Zwischen den Stationen gibt es erhebliche Unterschiede hin-
sichtlich des Wissens über das Fatigue-Syndrom., wobei das Wissen dort
größer eingeschätzt wird, wo bereits eine Fatigue-Beratung durch das PIZ
erfolgt/e.
Insgesamt gesehen geben jedoch nur 13,1% der Antwortenden – und
zwar unabhängig von ihrer Berufserfahrung – an, sehr gutes oder gutes
Wissen zum tumorbedingten Fatigue-Syndrom zu besitzen.
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Bei der Einschätzung, wie viele Patientinnen und Patienten ein Fa-
tigue-Syndrom entwickeln, gibt es erhebliche Unterschiede in den Abtei-
lungen: Insgesamt gesehen glauben die Befragten, dass weniger als die
Häle der Patientinnen und Patienten Fatigue-Symptome zeigen. Dabei
verlassen sich die Befragten überwiegend auf die eigene Einschätzung,
Screeninginstrumente werden selten genutzt.
Insgesamt gesehen sind die Beratungsmöglichkeiten des PIZ in Bezug
auf das Fatigue-Syndrom nur bei ca. 30% aller Befragten bekannt, wobei
hier ein deutlich höherer Bekanntheitsgrad in den Kliniken vorliegt, in
denen bereits eine Beratung erfolgt.
Fazit: Der Wissenstand zum ema Fatigue muss ausgebaut werden.
Quellenangaben:
1. FIBS- Fatigue individuell bewältigen
250
Die Rolle von Krebserkrankungen bei der Langzeitpege
durch Angehörige
Katharina Gramann-Weschke 1, 2; Annegret Paelecke 2
1Fakultät für Gesundheitswissenschaften, gemeinsame Fakultät der
Brandenburgischen Technischen Universität Cottbus - Senftenberg, der
Medizinischen Hochschule Brandenburg Theodor Fontane und der Universität
Potsdam
2AOK Pege Akademie, AOK Nordost-Die Gesundheitkasse, Berlin, Deutschland
Zweck: Die Versorgung bei Pegebedürigkeit erfolgt in Deutschland
meistens durch Angehörige, nur teilweise unterstützt durch ambulante
Pegedienste und nur rund 25% in stationären Einrichtungen. Sie haben
somit in der pegerischen und sorgenden Begleitung in der häuslichen
Umgebung eine besondere Rolle. Zur Unterstützung dieser Situation ha-
ben Pegekassen nach §45 SGB XI den Aurag Pegekurse anzubieten,
in denen man praktische Pege und weitere Pegekompetenzen lernen
kann. Für Pegekassen ist von besonderem Interesse, ob für diese Kurse
zukünig besondere Aspekte der Pege von Menschen mit einer Krebser-
krankung zu berücksichtigen sind. Da schon lange nicht mehr jede Kreb-
serkrankung tödlich verläu, aber trotz guter Heilungschancen Spuren
hinterlässt, ist sie nicht mehr nur für die Akutpege, sondern auch für die
Langzeitpege von zunehmender Bedeutung. Neue Angebote zu onkolo-
gischen emen und zur Begleitung von Sterben und Tod sollen ggf. im
Spektrum der Pegekurse ergänzt werden.
Methoden: Pegebedürigkeit wird über einen Leistungsanspruch zur
Unterstützung in der Pegesituation über die Pegekassen erfasst. Die
Voraussetzung ist nach Antragstellung die Zuordnung eines Pegegrades.
Die Daten der AOK Nordost zur Pegebedürigkeit der Pegekasse
wurde in Verbindung mit Krebsdiagnosen aus der Krankenkasse be-
trachtet. Ergänzt wurden diese durch den jeweiligen Versorgungsort zum
Lebensende.
Ergebnisse: Bei der AOK Nordost gab es 2018 n=47.399 Pegebedürige
mit einer Krebsdiagnose. Von diesen werden 23% stationär, 42% zu Hause
ohne und 36% zu Hause mit Pegedienst versorgt. Ein Drittel davon sind
im Laufe des Jahres 2018 verstorben. Davon sind 2/3 der zu Hause Gep-
egten auch zu Hause gestorben.
Fazit: Es wird daher ein Bedarf gesehen, die Pege von Menschen mit
Krebserkrankungen und zur Begleitung am Lebensende, als emen für
zukünige Pegekurse für Angehörige zu implementieren.
Quellenangaben:
1. Daten zu Versicherten der AOK Nordost - Die Gesundheitskasse 2018
Oenlegungserklärung: kein Interessenskonikt
340
Pegerisches Beratungsprogramm in der ambulanten
Nachsorge stammzelltransplantierter Patienten
Norbert Hebestreit
Universitätsklinikum Jena, Pegedirektion, Jena, Deutschland
Purpose: Um angemessen auf das Problemprol stammzelltransplantierter
Patienten reagieren zu können, wurde ein pegerisches Beratungspro-
gramm entwickelt (6 Module): (1) Körperpege, (2) Aktivität/Ruhe, (3)
Ernährung/Sicherheit, (4) erapiekooperation, (5) Soziale Interaktion
und (6) Integrität der Person. Ziel der Studie ist es, die Wirksamkeit des
Programms zu überprüfen.
Methods: Das Programm soll sich fördernd auf die (a) Selbstpegekom-
petenz der Patienten auswirken, deren (b) Pegeabhängigkeit senken und
die (c) individuelle Lebensqualität steigern. Die Intervention wird über
eine RCT evaluiert. Die Interventionspatienten (IG) nehmen am komple-
mentären Beratungsprogramm teil. Die Kontrollpatienten (KG) werden
kliniküblich versorgt. Für alle drei Studienendpunkte (a, b, c) werden zur
Entlassung (T1), nach 3 Monaten (T2) und nach 6 Monaten (T3) Mess-
werte (ASA-A, PAS, SEIQoL-DW) erfasst.
Results: 62 Patienten wurden in die Studie aufgenommen. Die Ergebnisse
belegen von T1 nach T3 einen größeren Anstieg der Selbstpegekompe-
tenz (ASA-Punkte: IG 8,9 vs. KG 0,1; P < 0,01) und einen stärkeren Abfall
der Pegeabhängigkeit (PAS-Punkte: IG 8,5 vs. KG 4,4; P < 0,01) unter In-
tervention. Eekte bezüglich der Lebensqualität waren nicht nachweisbar.
Conclusions: Die Studienergebnisse bestätigen die positiven Auswirkun-
gen der Pegeberatung auf das Patientenoutcome. Damit werden Unter-
suchungsergebnisse unterstützt, welche den Nutzen vergleichbarer Inter-
ventionen in der Intermediär- und Spätphase nach HSCT belegen. Zur
Ergebnisbekräigung gilt es, Replikationen in größeren Stichproben zu
planen.
Disclosure Statement:
1. Anstellungsverhältnis oder Führungsposition
Keine
2. Beratungstätigkeit
Keine
3. Aktienbesitz
Keine
4. Honorare
Keine
5. Finanzierung wissenschalicher Untersuchungen
Keine
6. Gutachtertätigkeiten
Keine
7. Andere nanzielle Beziehungen
Keine
605
Pegerische Interventionen bei einem Hand-Fuß-Syndrom
bedingt durch eine Target- oder Chemotherapie: Eine
systematische Literaturübersicht
Nino Chikhradze 1; Sara Marquard 2; Melanie Pieper 3; Tabea Büter 3;
Dauer Bettina 4; Birgit Kröger 5; Gabriele Knötgen 6; Patrik Ristau 7;
Kerstin Schröder 8; Stefanie Seeling 9
1Ruhr-Universität Bochum, Bochum, Deutschland
2Universität Osnabrück, Osnabrück, Deutschland
3Krankenhaus Ludmillenstift, Meppen, Deutschland
4Philosophisch-Theologische Hochschule Vallendar, Vallendar, Deutschland
5Katholisches Krankenhaus Hagen gem. GmbH, Hagen, Deutschland
6Ubbo-Emmius-Klinik, Aurich, Deutschland
7Johanniter-Unfall-Hilfe e.V. Regionalverband Darmstadt-Dieburg
8Klinikum Bremen-Mitte, Bremen, Deutschland
9Hochschule Osnabrück – Campus Lingen, Lingen (Ems), Deutschland
Zweck: Menschen, die aufgrund einer onkologischen Erkrankung eine
Chemotherapie erhalten, leiden o unter einem Hand-Fuß-Syndrom
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts144
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2018
Index
2018
(HFS). In diesem Zusammenhang steigt die Bedeutung an unterstüt-
zenden Maßnahmen, die der Reduktion und Prophylaxe der Symptome
dienen. Diese internationale Literaturübersicht stellt die identizierten,
evidenzbasierten Pegeinterventionen bei einem HFS dar.
Methoden: Eine systematische Literaturrecherche erfolgte in Literatur-
datenbanken aus unterschiedlichen Disziplinen für den Zeitraum 01.2010
– 09.2019. Eingeschlossen wurden deutsch- oder englischsprachige wis-
senschaliche Publikationen. Die Qualitätsbewertung sowie Analyse
und Synthese der Studien, erfolgte von den Mitgliedern der Sektion der
Deutschen Gesellscha für Pegewissenscha e. V.
Ergebnisse: Für die Qualitätsbewertung konnten n=38 Publikationen in
die systematische Literaturübersicht eingeschlossen werden. Die Haupt-
themen der Literaturanalyse waren zum einen, allgemeine Vorgehens-
weisen pegerischer Intervention in der Prävention und Behandlung und
zum anderen spezische Planung von präventiven Maßnahmen je nach
erapieregime bzw. Medikamentengabe.
Fazit: Die Prävention und die Behandlung von HFS in der onkologischen
erapie ist in der Literatur sichtbar. Die Umsetzung dieser Interven-
tionen in der direkten Interaktion und durch edukative Konzepte sind
elementar für die bildende und begleitende Rolle der Pegefachkra.
Grundlage hierfür bilden therapienagepasste Interventionen sowie gute
kommunikative und agogische Kompetenzen der Pegenden.
Quellenangaben:
1. Bartal A, Mátrai Z, Szûcs A, Liszkay G.(2011). Main treatment and preventive
measures for handfoot syndrome, a dermatologic side eect of cancer therapy.
Magy Onkol.:91-8.
2. Fabbrocini G, Cristaudo A, Ionescu MA, Panariello L, Robert G, Pellicano M,
Ayala F. (2018). Topical non-occlusive polymers in hand-foot syndrome. G Ital
Dermatol Venereol;153(2):165-171.
Oenlegungserklärung: Es sind keine relevanten nanziellen Verbindungen
oenzulegen.
616
Versorgung von Patienten mit kolo-rektalem Karzinom:
Der Einsatz einer „Advanced Nursing Practice“ (ANP) Als
ergänzende Praxisoption
Roland Jusu Allieu
Münster, Deutschland
Purpose: Jährlich steigt die Zahl der diagnostizierten und behandelten
Patienten mit kolo-rektalem Karzinom. Um den Bedürfnissen dieser
Patienten gerecht zu werden, werden sie durch ein spezialisiertes inter-
disziplinäres Team versorgt, das auf eine systematische Beratung, Diag-
nostik, Behandlung und Nachsorge abzielt. Um die Behandlung dieser
Patienten auf pegerischer Seite zu optimieren, könnte eine „Advance
Nursing Practice“ (ANP) eingeführt werden. Dies erfordert jedoch eine
strategische Entwicklung, Implementierung und Evaluation dieses Ver-
sorgungskonzeptes und -modells. Das PEPPA-Framework bietet ein
Modell dafür. Gut funktionierende Konzepte oder Modelle sollen in die
Praxis umsetzen und durch weitere Forschung optimiert werden.
Das Ziel ist die Identizierung und Zusammenfassung von Tätigkeits-
feldern einer ANP im Rahmen der Versorgung von Patienten mit ko-
lo-rektalem Karzinom.
Methods: Zu diesem Zweck wurde eine systematische Literaturrecherche
in CINAHL durchgeführt. Diese ergab 22 Studien. Anhand der Abstrakte
konnten vier geeignete Studien identiziert werden, in welchen die Be-
deutung der ANP in der Patientenversorgung deutlich wurde, dennoch
fokussierten sich nur zwei auf das kolo-rektale Karzinom.
Results: Die Komplexität der Patientenversorgung und der Krank-
heitsverlauf und die Bedeutung eines multidisziplinären Teams setzt die
Entwicklung neuer Versorgungsmodelle voraus, wie zum Beispiel die Ein-
führung der ANP.
Conclusions: Eicher et. al. 2006 weisen darauf hin, dass ANP Interven-
tionen einen positiven Einuss auf die Patientenversorgung haben kann.
Dennoch mangelt es an primären Evidenzen hinsichtlich der Versorgung
von Patienten mit kolo-rektalem Karzinom.
765
Sensibilisierung von Pegenden auf tägliche Phänomene.
Eine Prozessoptimierung am Beispiel orale Mucositis
Timo Gottlieb
Universitätsmedizin Essen, Uniklinikum Essen, Essen, Deutschland
Zweck: Der Zweck dieser Arbeit ist die Sensibilisierung der Pegefach-
personen auf ihre Kernkompetenzen und die Abbildung dieser Ergeb-
nisse in Rahmen von sichtbaren Instrumenten. Hierbei soll der Pege die
Möglichkeit gegeben werden, Erfolge zu zeigen und diese präsentieren zu
können.
Methoden: Methodisch wurde in mehreren Schritten vorgegangen. Zu-
nächst wurde eine Literaturanalyse zum ema Orale Mucositis durch-
geführt und die neusten Erkenntnisse zusammengetragen. Im nächsten
Schritt wurde das Assessmentinstrument „Oral Mucositis Dayli Ques-
tionare“ durch die Pege ausgewählt und entsprechend in die Praxis im-
plementiert. In einer ersten Pilotphase von Vier Wochen wurde dies ge-
testet und dann evaluiert und anschließend ausgeweitet. Im letzten Schritt
wurden Fortbildungen in Form von „One Minute Wonder“ erstellt sowie
getestet und evaluiert.
Ergebnisse: Für die Pege hat sich schnell eine Zufriedene Haltung en-
twickelt, ihre Qualikationen abbilden zu können. Ebenso wurde im
interdisziplinären Kontext eine hohe Akzeptanz erreicht und das As-
sessment für die tägliche Visite zur Evaluation genutzt. Das Assessment
konnte mit wenigen Veränderungen eingeführt werden und hatte eine
leichte Anwendungsmöglichkeit.
Fazit: Als Fazit lässt sich deutlich aufzeigen, dass die Pege sich durch
Visualisierung der eigenen Ergebnisse motivieren lässt, sich diesem
Phänomen zu widmen und entsprechend an der Weiterentwicklung
mitzuarbeiten. Durch die Mitbestimmung an der Auswahl von Assess-
ment und emen für die OMW wird eine hohe Akzeptanz erwartet. Das
ema hat auch interdisziplinär einen anderen Stellenwert erreicht, wofür
die Pege Vorreiter ist.
Quellenangaben:
1. Leitlinienprogramm Onkologie (Deutsche Krebsgesellscha, Deutsche
Krebshilfe, AWMF): Supportive erapie bei onkologischen PatientInnen -
Langversion 1.1, 2017,
AWMF Registernummer: 032/054OL, http://leitlinienprogramm- onkologie.
de/Supportive-erapie.95.0.html (Zugri am 07.09.2019)
Oenlegungserklärung: Der Autor erklärt hiermit, keinen Interessenskonikt zu
haben
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 145
Inhalt
2018
Index
2018
786
Basale Stimulation in der Onkologie. Wer protiert davon?
Anja Köhler
Universitätsklinikum Jena, KIM II, Abt. Palliativmedizin, Jena, Deutschland
Viele der Patienten mit denen wir täglich arbeiten, sind hoch betagt
oder leiden unter dementiellen Veränderungen. Sie haben cerebrale Me-
tastasen oder Tumoren des ZNS, sind durch einen Aufenthalt auf einer
Intensivstation beeinträchtigt, haben ein Delir, eine schwere Infektion,
Elektrolytverschiebungen oder benden sich am Lebensende. Es gibt aber
auch Patienten, welche aufgrund ihrer Fatigue oder ihrer ausgeprägten
körperlichen Schwäche tagsüber wie auch nachts schlafen. Alle haben sie
o eins gemeinsam: Sie verlieren die Orientierung. Der Alltag hat ein-
en ungewohnten Rhythmus, viele fremde Menschen sind um sie herum,
unbekannte Prozeduren müssen durchgeführt werden, der Lebensmittel-
punkt ist das Krankenbett. Der Patient und seine Angehörigen benötigen
in dieser krisenhaen Lebenssituation Unterstützung durch Pegende. In
diesem Vortrag möchte ich das Konzept der Basalen Stimulation® vorstel-
len und anhand von Beispielen, Möglichkeiten für eine kompetente und
empathische Pege und Begleitung dieser Menschen aufzuzeigen.
Psychooncology
Poster
26
Study on the Relationship between Patients with Advanced
Prostate Cancer and their Partners
Andreas Ihrig 1; Tobias Hanslmeier 1; Hans-Christoph Friederich 1;
Carsten Grüllich 2; Imad Maatouk 1
1Sektion Psychoonkologie, Universitätsklinik Heidelberg, Heidelberg,
Deutschland
2NCT, Universitätsklinik Heidelberg, Heidelberg
Purpose: e aim of the study is to identify possible dierences between
patients in an advanced stage of prostate cancer and their partners in the
areas of therapy decision, treatment goals, perception of cognitive chang-
es, stress and partnership. e results should contribute to a better under-
standing of this special life situation.
Methods: e study is a non-interventional explorative study. We inves-
tigated in 100 patients with advanced prostate cancer and their partners
who completed their own questionnaires. Anamnestic, psychological (dis-
tress thermometer, PHQ-4, EORTC:global quality of life, ASKU, PA-F)
and partnership (QMI-D) questionnaires are used.
Results: e partners are younger than the patients (64.6 vs. 69.2 years).
No signicant dierences were found in quality of life, subjective com-
petence expectation and depressiveness. However, the partners reported
higher distress (5.7 vs. 4.8), anxiety (1.9 vs. 1.4) and fear of progression
(33.9 vs. 30.8). Trends toward worsening are reported in all 13 questions
on core symptoms of dementia. e most pronounced deteriorations are
in the area of emotional balance, motivation to do something, to perform
movements correctly and to organize everyday things. Partners rate the
limitations in 9 of the 13 questions more highly than the patients them-
selves. With regard to the therapy decision, a decision based on partner-
ship is usually preferred, with the emphasis on the patient’s will. Only 6%
of the patients state that they make the therapy decision without involving
their partner. e quality of the partnership is rated better by the patients
(42.4 vs. 40.6) than by the partners.
Conclusions: Apart from the fact that both groups are psychologically
highly stressed, the partners show a pronounced anxiety symptomatology
while the patients suer from a deterioration of cognitive abilities. Due
to the high stress of these couples and the involvement of the partners in
the therapy decision, it is important that the attending physician provides
detailed information and support to both.
Disclosure Statement: None
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65
Identifying Subtypes of the Psycho-Neurological Symptom
Cluster in Long-Term Prostate Cancer Survivors – Results from
the Multiregional Procas Study
Salome Adam 1; Melissa S.Y. Thong 2; Eva Martin-Diener 3; Bertrand
Camey 4; Celine Egger Hayoz 4; Isabelle Konzelmann 5; Seyed Mohsen
Mousavi 6, 7; Christian Herrmann 6, 7; Sabine Rohrmann 8; Miriam Wanner 8;
Katharina Staehlin 9; Räto Strebel 10; Marco Randazzo 1; Hubert John 11;
Hans-Peter Schmid 12; Anita Feller 1; Volker Arndt 1, 2
1National Institute for Cancer Epidemiology and Registration (NICER), Zurich,
Schweiz
2Unit of Cancer Survivorship, German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
3Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and
Prevention Institute, University of Zurich, Zurich, Schweiz
4Fribourg Cancer Registry, Fribourg, Schweiz
5Health Observatory Valais, Valais Cancer Registry, Sion, Schweiz
6Cancer Registry East Switzerland, St. Gallen, Schweiz
7Cancer Registry Graubünden and Glarus, Chur, Schweiz
8Cancer Registry Zurich and Zug, Zurich, Schweiz
9Basel Cancer Registry, Basel, Schweiz
10Department of Urology, Graubünden Cantonal Hospital, Chur, Schweiz
11Department of Urology, Winterthur Cantonal Hospital, Winterthur, Schweiz
12Department of Urology, St. Gallen Cantonal Hospital, St. Gallen, Schweiz
Purpose: Aside from common urological and sexual problems, long-term
(≥5 years aer diagnosis) prostate cancer (PC) survivors might suer from
pain, fatigue and depression. ese symptoms are collectively known as
the psycho-neurological symptom (PNS) cluster. No research has been
done to 1) identify possible subtypes of this cluster, 2) classify cancer sur-
vivors accordingly, and 3) explore associations between subtypes of the
PNS cluster and health-related quality of life (HRQoL) in long-term PC
survivors.
Methods: e study sample included 653 stage T1-T3N0M0 long-term
PC survivors, identied from the multiregional Prostate Cancer Survi-
vorship in Switzerland study. Briey, in 2017/2018, PC survivors were
identied via six population-based cancer registries based in both Ger-
man- and French-speaking Switzerland. Fatigue was assessed with the
EORTC QLQ-FA12, mental health with the MHI-5, and pain with the
EORTC QLQ-C30 questionnaire. Latent class analysis was used to derive
PNS cluster classes. Factors associated with the derived classes were deter-
mined with multinomial logistic regression analysis.
Results: ree PNS classes were identied: class 1 (n=394, 61.4%) – ‘low
pain, physical and emotional fatigue, moderate mental distress’; class 2
(n=98, 15.1%) – ‘low physical fatigue and pain, moderate emotional fa-
tigue, high mental distress’; and class 3 (n=151, 23.5%) high scores for all
symptoms. Survivors in class 2 and 3 were more likely to be less physical-
ly active, having a comorbidity, being treated with radiation therapy, and
having worse HRQoL outcomes compared to class 1 (reference).
Conclusions: ree distinct classes of the PNS cluster were identied,
which could be distinguished by treatment, comorbidities, lifestyle factors
and HRQoL outcomes. erefore, improving classication of PC survi-
vors according to severity of multiple symptoms could assist in developing
interventions tailored to survivors’ needs.
Disclosure Statement: e authors have nothing to disclose.
71
Expectations and Experiences with the term
“Immunotherapy” in the Context of Cancer
Jennier Richter; Andreas Ihrig; Imad Maatouk
Heidelberg, Division of Psychooncology, Department of General Internal
Medicine and Psychosomatic, University Hospital Heidelberg, Heidelberg,
Deutschland
Purpose: e aim of our study was to describe expectations and expe-
riences of patients, physicians and employees of the cancer information
service with immune checkpoint inhibitors (ICIs) in cancer therapy.
Methods: In this mixed methods study we investigated knowledge, ideas
and believes of 108 cancer patients and 53 patients without cancer about
ICIs. For this purpose we used a structured questionnaire. We also inter-
viewed 12 patients which were currently receiving ICI therapy. In order to
examine the health professionals´ perspective we performed focus groups
with 8 physicians and 9 employees of the cancer information service.
Results: In the patient groups we could identify a lack of knowledge re-
garding the ICIs. 38% of the patients with ICI therapy were not able to
describe the mechanism of the therapy without relevant false contents. In
patients without ICI therapy this percentage was even 87%. Furthermore,
the results suggest that the image of immunotherapy is noticeably better
than that of CT. Immunotherapy is considered to be more expensive, but
also in lesser time, more promising and with a lower spectrum of side
eects. In patients´ opinion, the future rather belongs to immunothera-
py than to CT. In the qualitative interviews, the patients focused on the
topics “prognosis, “quality of life, “therapy decision” and “side eects.
e participants of the focus groups discussed more about topics such as
creation of an information base” and “how immunotherapy is portrayed
in the media.
Conclusions: Personal conversation between patients and physicians
should have the highest priority to create an information base for the pa-
tient. Furthermore, evidence-based tools, which provide information on
ICIs to patients, would be desirable. Based on the good rating of the ICI
therapy, it might be useful during therapy education to ensure that possi-
ble side eects are not underestimated by the patients.
Disclosure Statement: ere are no nancial conicts of interest to disclose.
93
Loh-Fear: Determination of Subjectively Perceived Anxiety of
Patients inOncological Abdominal Surgery
Benedikt Kunzmann 1; Jan Brederecke 2; Lea Harms 3; Thomas Jungbluth 1;
Tanja Zimmermann 2; Jens Harms 1
1Klinik für Allgemein- und Viszeralchirurgie, Klinikum Wolfsburg, Wolfsburg,
Deutschland
2Klinik für Psychosomatik und Psychotherapie, Mediznische Hochschule
Hannover, Hannover, Deutschland
3Columbia University New York, Department of Obestetrics and Gynecology,
New York, United States
Purpose: For many patients visceral oncological surgery is associated with
anxiety, such as fear of heteronomy, pain, injury, physical disgurement,
complications and death. e present study measures anxiety in patients
both in intensity and over time.
Methods: In N= 100 persons with a malignant gastrointestinal tumor (62
men, 38 women; age: M = 68.4 years; SD=10.8; 36-89) anxiety, depression
and distress was assessed at 4 time points: rst contact (T1), inpatient ad-
mission (T2), hospital discharge (T3) and 30 days post inpatient discharge
(T4).
Results: Subjectively perceived anxiety and depression was highest at T1
and at T3. 30% of patients showed increased values above the cut-o, re-
garding anxiety and depression at T1. Higher values of fear at T1 did not
correlate in regards to levels of fear at T4 in comparison with patients ex-
hibiting low values of fear at T1. In the framework of a logistical regression
a high subjectively perceived burden at T1 was attached to elevated levels
of fears at T3 and T4. A multifactor analysis was performed.
Conclusions: Anxiety and depression appear to be an ongoing problem.
e identication of persons at risk for clinically relevant anxiety or de-
pression is a particular challenge. Since the extent of anxiety varies over
time, a one- o assessment of anxiety at the beginning is not sucient.
However, the subjectively perceived level of distress seems to be a valid
predictor for anxiety at the end of treatment. In the course of treatment,
the highest anxiety and depression values were found at initial contact and
inpatient discharge. Reasons for a lower expression during the treatment
phase may be due in the medical and nursing care and competence and
the subjective feeling of “being cared for”. e results verify the relevance
of screening tools for psychological burden also in oncological visceral
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surgery. Furthermore the question arises as to which psycho- oncological
interventions appear to be indicated and feasible in the pre- and periop-
erative setting.
Disclosure Statement: e authors declare that they have no conict of interest.
144
Benet-Finding in Long-Term Prostate Cancer Survivors
Irène Lassmann 1; Andreas Dinkel 2; Birgitt Marten-Mittag 2;
Helga Schulwitz 1; Jürgen E. Gschwend 1; Kathleen Herkommer 1
1Klinik und Poliklinik für Urologie, Technische Universität München, Fakultät für
Medizin, Klinikum rechts der Isar, München, Deutschland
2Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,
Technische Universität München, Fakultät für Medizin, Klinikum rechts der Isar,
München, Deutschland
Purpose: Benet-nding (BF) refers to positive eects that may arise in
the aermath of a cancer diagnosis. It involves disease-induced changes in
dierent aspects of personal and social life such as enhanced interpersonal
relationships or growing acceptance of lifes deciencies. e aim of the
current study was to investigate the extent of BF and its determinants in
prostate cancer (PC) survivors.
Methods: 4,252 PC survivors (97.9% radical prostatectomy) from the
German database “Familial PC” were available for analysis. Association
between BF (German version of the Benet-nding-scale) and sociode-
mographic and clinical variables was analyzed using bivariate analysis.
Results: Mean age at survey was 77.4±6.2 years with a mean follow-up of
14.8±3.8 years. 29.4% of the respondents owned a university degree, 85.4%
were living with a partner and 25.1% perceived the severity of the disease
as high. 19.6% had a biochemical recurrence at time of survey and 13.5%
were under PC-treatment. Mean BF-score was 3.1±1.0 (range 1-5), 59.7%
had a BF-score ≥3, 22.6% had score of ≥4. Highest BF-scores emerged for
the items “taught me to adjust to things I can`t change” (3.6±1.2), “has
helped me take things as they come» (3.6±1.2), and “has shown me that
all people need to be loved” (3.5±1.4). Higher BF-level was associated
with lower educational level and with higher perceived severity of the PC
(p<0.001). Time since diagnosis, biochemical recurrence, ongoing treat-
ment as well as anxiety and depression (patient health questionnaire-4)
showed statistically signicant but negligible associations with BF.
Conclusions: 60% of long-term PC survivors expressed moderate-to-high
levels of BF. Higher perceived severity of the disease as well as a lower ed-
ucational level were associated with higher levels of BF. In contrast, the
clinical course of the PC (past or present biochemical recurrence, ongoing
treatment) had no clinically meaningful eect on the amount of found
benet.
Disclosure Statement: No conict of interest.
151
Physical Exercize, Coping, and Survival in Cancer Patients
Volker Tschuschke 1; Elke Jäger 2; Margarete Ruppert 3
1Köln, Universitätsklinik, Köln, Deutschland
2Frankfurt am Main, Klinikum Nordwest, Frankfurt am Main, Deutschland
3Daimlerstraße 12, Palliativteam Hochtaunus, Bad Homburg, Deutschland
Purpose: A growing number of studies supports the positive connection
between physical exercise training programs and improved quality of life
in cancer patients. Some studies even suggest that an increased physical
activity may contribute to a better survival of such patients. We report
results of an exercise intervention program in patients by also controlling
for psychological and coping ressources with regard to survival time.
Methods: 82 patients with advanced cancer diseases of various kinds
received an individually tailor-made exercise training over six weeks.
Gain in lung capacity (VO2max) was controlled by comparing pre and
post VO2max. Patients completed the EORTC QLQ-C30 questionnaire,
Prole of Mood Scales (POMS), SCL-K and were interviewed with a semi-
structured interview with regard to their coping ressources at baseline
and aer the exercise intervention. Independent blind raters objectively
rated the interviews sentence by sentence using the Ulm Coping Manual
(UCM). Survival time was followed for more than eight years.
Results: Linear mixed-model analyses revealed that specic active cop-
ing ressources and sucient role functions predicted gain in VO2max and
VO2max in turn predicted survival time besides signicant increases in
two active coping dimensions: information seeking and anticipation.
Conclusions: Psychological and personality variables such as coping res-
sources are essential predictors for cancer patients’ benet from exercise
training.
208
Integration of Cross-Sectoral Psycho-Oncological Care into
Inpatient and Outpatient Cancer Therapy
Steen Krebs 1; Jennifer Benner 2; Lukas Matyschik 3; Karin Osborne 4;
Jürgen Wolf 1; Michael Kusch 1
1Centrum für Integrierte Onkologie - CIO Köln, Universitätsklinikum Köln, Köln
2GFO Kliniken Troisdorf, Standort St. Josef, Troisdorf
3Johanna-Etienne-Krankenhaus, Neuss
4Kliniken Mariahilf, Mönchengladbach
Purpose: e National Cancer Plan describes the objective of cross-sec-
tor, integrated oncological care (eld of action 2, objective 7). Coopera-
tion and coordination in oncological care across sectors and occupational
groups should be improved and self-help more closely integrated. e
isPO project (integrated, cross-sectoral psycho-oncology), funded by the
Innovation Committee of the Federal Joint Committee, aims to integrate
psycho-oncology into inpatient and outpatient care through vertical and
horizontal coordination and cooperation.
Methods: In the isPO project, a psycho-oncological care programme will
be developed, implemented and evaluated by 2021. e integration of the
programme into oncology will be implemented through the establishment
of psycho-oncological care networks consisting of an oncological centre
and registered doctors (vertical cooperation) as well as the (horizontal)
cooperation of doctors, nurses/medical assistants, psychotherapists, psy-
chosocial specialists and self-help. A network coordinator takes over the
central control of the processes and is the contact person for all profes-
sional groups.
Results: e program will be integrated at four locations (Cologne, Trois-
dorf, Neuss, Mönchengladbach) as part of a contract pursuant to § 140a
SGB V. It is presented in the form of organization charts with dened tasks
and powers and is implemented on the basis of formal administrative
SOP´s . e programme has been undergoing testing since the beginning
of 2019. It is evaluated and optimized within the framework of a qual-
ity management system. e main outcome criteria for integration are
(timely) patient enrolment and cross-sector networking of care.
Conclusions: e establishment of cooperation and coordination struc-
tures integrated into the oncological care routine is essential if all cancer
patients are to be oered psycho-oncological care, as required by the Na-
tional Cancer Plan.
References: not applicable
Disclosure Statement: e authors declare that they have no conict of interests.
231
Factors Inuencing Psychosocial Distress in Persons with
Hereditary Cancer Predisposition Syndromes and their
Relatives - “Gemeinsamgen
Josene Fischer-Jacobs 1; Anna Maria Kastner 1; Andrea Hahne 2;
Tanja Zimmermann 1
1Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical
School, Hannover, Deutschland
2BRCA Netzwerk e.V., Bonn, Deutschland
Purpose: Persons with hereditary cancer predisposition syndromes car-
ry a mutation in individual genes and hence are at increased risk for the
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development of specic tumors (e.g., HBOC, HNPCC, Gorlin Syndrome).
Typically the age of onset is earlier and a familial accumulation of the syn-
drome-specic tumor spectrum is seen. e knowledge of a genetic dispo-
sition can relieve aected families, providing the possibilities of prophy-
lactic surgeries and intensied surveillance for early detection. As well as
precipitate psychological stress. Specic factors that can lead to increased
distress involve, e.g., coping behavior, psychosocial problems, familial is-
sues, feelings of guilt and fear of developing cancer. Whether and to what
extent relatives experience distress has not yet been suciently investi-
gated. is study therefore aims to gain knowledge about stress inducing
factors in mutation carriers and relatives.
Methods: Within the scope of a nationwide, cross-sectional online sur-
vey mutation carriers and relatives will be asked about their subjectively
experienced psychological distress via patient reported outcomes N=236
individuals will be included. In addition, questionnaires are used to record
individual and family factors for which a correlation is assumed.
Results: For the statistical analysis we assume a nal N of 118 per group
(N=236). Besides descriptive evaluations, such as mean values, standard
deviations and frequencies, regression analyses are planned. First results
will be presented at the conference.
Conclusions: e research ndings can help towards identifying predic-
tors of psychosocial distress as well as determining specic risk groups.
Consequently, feasible decits in the quality of care can be detected. Fur-
thermore the results can be implemented in the development of further
psychosocial care services and interventions. In particular this study can
make an important contribution to assessing the psychosocial burden of
relatives, given that only little research on these individuals has been con-
ducted so far.
237
And Now, Am I Ill or Still Healthy?” Psychological and
Medical Need for Assistance in Women with Increased Risk
for Hereditary Breast- and Ovarian Cancer – A Qualitative
Analysis
Josene Fischer-Jacobs 1; Schlegelberger Brigitte 1; Martina de Zwaan 1;
Tanja Zimmermann 2
1Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical
School, Hannover, Deutschland
2Department of Human Genetics, Hannover Medical School, Hannover,
Deutschland
Purpose: Healthy women recognized to carry a pathogenic BRCA1/2 mu-
tation bear a signicant psychological burden, e.g. due to uncertainty how
to deal with an increased risk to develop breast (BC) and ovarian cancer
(OC). Mutation carriers may experience signicant levels of distress in the
short time, and genetic testing distress can remain elevated in the longer
term, especially among younger women and women with higher levels of
distress at testing. Only one-third of the counselees who reported a re-
quest for psychological assistance had attained help. is study aims to
identify whether, and if so, in which extent women with hereditary BC
and OC need psychological and medical assistance and which contents
could be additionally of interest for them.
Methods: N = 21 women were asked by in-depth interviews if a genetic
burden exists and if psychological assistance were requested. In addition,
topics of interest were identied. Moreover, N = 5 interviews were con-
ducted with experts (physicians, psycho-oncologists) to identify themes
of interest for women with a pathogenic mutation.
Results: Preliminary analysis indicates that 33.3% requested for psycho-
logical help because of the genetic mutation and/or their consequence in
the past (divorce, depression). Further, 52.4% of the interviewed women
show an interest in psychological help. At this point main topics are com-
munication within relatives, anxiety, decision-making processes, dealing
with genetic- and family-related distress. Relatives and their way to cope
with the mutation are of particular importance for aected people. More
extensive analyses are planned.
Conclusions: In particular this study takes rst step toward understanding
patients’ psychological and medical need for assistance and suggested
main themes of interest. A long-term goal could be the development of
further psychosocial care services and interventions. In Addition further
research is needed which focus on relatives, because whether and to
what extent relatives experience distress has not yet been suciently
investigated.
243
Spiritual Care in Oncology: Cancer Patients’ Unmet Spiritual –
Data from a Pilot Project
Arndt Büssing 1; Jens Büntzel 2; Eckhard Frick 3
1Professorship Quality of Life, Spirituality and Coping, Institute of Integrative
Medicine , Witten/Herdecke University, Herdecke, Deutschland
2Department of Otolaryngology, Palliative Care Unit, Südharz Clinic
Nordhausen, Nordhausen, Deutschland
3Research Unit Spiritual Care, Clinic for Psychosomatic Medicine and
Psychotherapy, Technical University Munich, München, Deutschland
Purpose: As part of the AG PRIO project on spiritual needs of cancer
patients, we analyzed their unmet spiritual needs and related these to their
interpretations of illness (IoI) and quality of life.
Methods: Cross sectional survey in a dened time frame among patients
with cancer (N=171; 62% women; 61±12 years of age; 53% R-S-) from
centers in East and West Germany with standardized questionnaires. Un-
met spiritual needs (SpNQ-20) were categorized as Religious (RN), Exis-
tential (ExN), Inner Peace (IPN), Generativity (GN) needs with intensity
scores ranging from 0 to 3.
Results: RN (0,8±0,9) and ExN (0,8±0,8) scored low, IPN (1,6±0,9) and
GN (1,4±0,9) higher. ere were no signicant dierences between East
and West. eir needs were moderately (r 0.3-0.5) related to positive IoI,
while negative IoI were related moderately to ExN and IPN only. IPN were
weakly (r 0.2-0.3) related to lower wellbeing (WHO5) and life satisfaction
(BMLSS-10), and positively with under pressure feelings (VAS); RN and
GN were not signicantly related. Patients with higher tumor stages had
signicantly higher ExN, IPN and GN, but not RN.
Conclusions: Identifying cancer patients´ unmeet spiritual needs requires
a reaction from health professionals and pastoral workers. ese needs
were related to higher tumor stages, how they perceive their illness and
lower wellbeing - but not RN. us, health professionals do not have to
fear responding to strictly religious issues they may feel less competent
to address.
Disclosure Statement: e study was supported by a grant of German Cancer
Society. e authors disclose any conict of interest.
246
Dimensionen Der Patientenkompetenz Bei Krebsbetroenen:
Ergebnisse Einer Replikationsstudie im Vergleich
Juergen M. Giesler 1; Christine Holmberg 2; Joachim Weis 3
1Sektion Versorgungsforschung und Rehabilitationsforschung,
Universitätsklinikum Freiburg, Freiburg, Deutschland
2Institut für Sozialmedizin und Epidemiologie, Medizinische Hochschule
Brandenburg Theodor Fontane, Brandenburg an der Havel, Deutschland
3Stiftungsprofessur Selbsthilfeforschung, Tumorzentrum/CCC Freiburg,
Universitätsklinikum Freiburg, Freiburg, Deutschland
Purpose: Advancing Patient Competence (PC) represents an important
goal of Germany’s National Cancer Plan. However, no consensus has yet
been reached as to which dimensions may constitute PC. erefore, this
study asked whether the 8 dimensions of PC derived by Giesler and Weis1
would replicate in other samples of cancer patients.
Methods: Based on a sample of N = 424 breast, colorectal, and prostate
cancer patients (mean age 62 years, 53% female) undergoing either on-
cological rehabilitation or treatment in specialized oncology practices,
conrmatory factor analyses were performed for the problem- and the
emotion-focused items of the Patient Competence Questionnaire 57.1
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Results: Using conventional t criteria, 7 factors were identied for prob-
lem-focused items (e.g. seeking information, self-regulation, and assert-
ively interacting with physicians; CFI = .921, RMSEA = .054). For emo-
tion-focused items 3 factors were identied (managing distress, dealing
with threat, and (low) avoidance; CFI = .961, RMSEA = .055).
Conclusions: is study partially conrms the dimensions of PC found
by earlier research.1 Studies of similar intent report comparable results, in-
cluding a splitting of factors.2,3us, the factors listed in the results section
appear to be replicable dimensions of PC with some restrictions. Future
research should focus on renements of the concept of PC and on inter-
ventions to advance it.
References:
1 Giesler JM, Weis J. Developing a self-rating measure of patient compe-
tence in the context of oncology: a multi-center study. Psychooncology.
2008;17(11):1089-1099.
2 Ralf L. Konrmatorische Überprüfung der dimensionalen Struktur des FEPK-
57 bei Patienten mit Prostatakrebs und Patientinnen mit Brustkrebs. Freiburg/
Br.: Pädagogische Hochschule Freiburg;2015.
3 Giesler JM, Holmberg C, Müller-Nordhorn J, Weis J. Conrmatory Factor
Analyses of the Patient Competence Questionnaire 57 in a Sample of Colorec-
tal Cancer Patients. Freiburg/Br.: Medical Center, University of Freiburg; 2019.
Disclosure Statement: e authors have no conict of interest.
268
Correlation of Psychooncological Support and Quality of Life
in Patients with Oral Cancer: A Study Based on an Electronic
Psychooncological Screening Instrument and Quality of Life
Questionnaire
Sebastian Hoefert 1; Norbert Schäeler 2; Martin Wickert 2; Siegmar
Reinert 1
1Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie,
Universitätsklinikum Tübingen, Tübingen
2Psychosomatische Medizin und Psychotherapie, Universitätsklinikum
Tübingen, Tübingen, Deutschland
Purpose: Cancer patients suer from severe distress, and oral cancer pa-
tients report some of the highest distress levels of all cancer patients1. e
German S3-Guidline and the certied Head and Neck Cancer Centres
recommend psychooncological support for these patients. is study ana-
lysed the need for psychooncological support with an electronic screening
instrument (ePOS) and measured the Quality of Life (QoL) up to one year
aer therapy.
Methods: e ePOS instrument included the DISTRESS questionnaire
(DT), the Hornheider Screening Instrument (HSI), Hospital Anxiety and
Depression Scale (HADS), and inquiries for personal support need. ese
patients were also monitored with the EORTC QLQ-C30 and H&N35
QoL questionnaires.
Results: A total of 66 patients were screened including 37 patients with
QoL surveys completed aer one year: 76% of patients reached the
pre-therapeutic QoL level. Patients who opted for psychooncologial sup-
port had a signicantly worse QoL aer one year compared to patients
who tested positive for treatment need but did not request psychoonco-
logical support. e HADS was a predictive marker for a lower QoL aer
1 year.
Conclusions: Generally, a positive ePOS test for psychooncological sup-
port was not a signicant predictor for lower QoL outcome aer one year.
Patients who requested support showed a lower outcome in QoL. Con-
sequently, these patients should be supported more intensively. Patients
with a positive HADS may also benet from more intensive psychoonco-
logical support2. Our study was one of the rst analysing the pre-thera-
peutic distress and QoL outcome aer surgical cancer treatment.
References:
1. Dunne S et al. Psychological variables associated with quality of life following
primary treatment for head and neck cancer: a systematic review of the litera-
ture from 2004 to 2015. Psychoncology 26:149-160 (2017)
2. Handschel J et al. Psychological aspects aect quality of life in patients with
oral squamous cell carcinomas. Psycho-Oncology 22: 677-682 (2013)
Disclosure Statement: Nothing to disclose
304
Prognostic Awareness Regarding the Treatment Intensity in
Cancer Patients
Filipa Krolo 1; Martina Preisler 2; Meike Watzlawik 1; Amy Rohrmoser 3;
Ute Goerling 3; Anne Letsch 2
1Sigmund Freud PrivatUniversität Berlin, Fakultät für Psychologie, Berlin,
Deutschland
2Charité Universitätsmedizin Berlin Campus Benjamin Franklin, Medizinische
Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie,
Berlin, Deutschland
3Charité – Universitätsmedizin Berlin, Charité Coprehensive Cancer Center,
Berlin, Deutschland
Purpose: Higher levels of patients´ prognostic awareness (PA), crucial
for early integration of palliative care in oncology, lead to better decision
making about further treatment and care options. However, previous
studies have found mostly low levels of PA in patients. Focussing on PA
regarding the treatment intensity (PATI) as one facet of PA, the patients´
perception of the treatment intensity and possible discrepancies between
them and their oncologists regarding PA were explored.
Methods: Five cancer patients of a large German university hospital
were interviewed about their perception of the treatment intensity. e
interviews were analysed with Kuckartz´s thematic content analysis. e
patients and their oncologists completed questionnaires assessing the pa-
tients’ PA, too.
Results: e questionnaires showed moderate to high levels of congru-
ence between patients’ and oncologists’ answers, indicating moderate to
high levels of PA in patients. e following factors were reportedly im-
pacting their perception of the treatment intensity: the physical condition,
hope for recovery and normality, conditions in the hospital, interaction
with oncologists, social and nancial factors and psychological condition.
Conclusion: Knowing the patients´ individual background and their per-
ception of the treatment intensity is a key factor for improving PATI. e
factors inuencing the perception of treatment intensity can be assessed
via tailored questions. If healthcare professionals address these topics,
they may meet specic communication needs of the patients, leading to
higher levels of PATI.
References:
1. Applebaum AJ, Kolva EA, Kulikowski JR, et al (2014) Conceptualizing prog-
nostic awareness in advanced cancer: A systematic review. J Health Psychol.
9:1103–1119.
2. Temel JS, Greer JA, Muzikansky A, et al (2010) Early palliative care for patients
with metastatic nonsmall-cell lung cancer. N Engl J Med 363:733–42.
3. Kuckartz, U (2007) Einführung in die computergestützte Analyse qualitativer
Daten. VS Verlag, Wiesbaden.
Disclosure Statement: No conicts of interest.
375
Development and Evaluation of an Unguided Psychosocial
Online-Intervention for Caregivers of Cancer Patients (OAse):
Results of a Feasibility Study
Miriam Grapp 1, 2; Johanna Ell 1; Hans-Christoph Friederich 2;
Imad Maatouk 1, 2
1Universitätsklinikum Heidelberg, Psychonkologische Ambulanz am Nationalen
Zentrum für Tumorerkrankungen, Heidelberg, Deutschland
2Universitätsklinikum Heidelberg, Klinik für Allgemeine Innere Medizin und
Psychosomatik, Heidelberg, Deutschland
Purpose: Informal caregivers (family and friends) of cancer patients pro-
vide support to the patient and at the same time they experience an in-
creased burden or distress - oen unprepared for their caregiving role.
Due to shame, uncertainty or lack of time, psychosocial face-to-face ser-
vices are rarely used by cancer caregivers. e aim of this study is therefore
to develop and evaluate an unguided psychosocial online-intervention for
caregivers of cancer patients (OAse).
Methods: From June 2018 to April 2019, n=41 caregivers of cancer pa-
tients (spouse, children, friends) were included in the study. Participation
in the study was independent of patients’ tumour site and treatment stage.
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OAse is a resource-oriented, web-based unguided self-help program com-
prising four modules (understanding and providing eective support, un-
derstanding the patient’s feelings, dealing with own burdensome feelings,
strengthening own resources). Qualitative and quantitative data were col-
lected at the beginning (T1) and at the end (T2) of the intervention to
assess the feasibility and acceptance of OAse as well as patient satisfaction
with the program.
Results: Of the 41 caregivers 65,9% (n=27) were female. Most of the par-
ticipants were spouses (70,7%, n=29), followed by adult children (19,5%,
n=8) and friends (9,8%, n=4). e age of participants ranged from 19 to
69 years (M=44,59, SD=13,75). Of the 41 participating caregivers, n=28
(62.2%) fully completed the OAse intervention. e qualitative and quan-
titative data show a high degree of caregivers’ satisfaction.
Conclusions: Up to now specialised psychological internet interventions
for caregivers of cancer patients are rare. In the present study OAse has
proven feasible and acceptable. Compared to other unguided online
interventions in this eld, the completion rate was very high. erefore,
the intervention could make a signicant contribution to improve
caregivers’ psychological condition and to increase their competency and
self-ecacy.
Disclosure Statement: Authors have no conicts of interests.
408
Is the Spectrum of Mental Disorders in Cancer (Ca) Patients
Changed by Time?
Michael Brinkers 1; Anne-Marie Toeper 2; Giselher Pfau 1; Frank Meyer 3
1Klinik für Anästhesiologie und Intensivtherapie Uni Magdeburg,
Schmerzambulanz, Magdeburg, Deutschland
2Klinik für Augenheilkunde, Uni Magdeburg, Magdeburg
3Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie, Uni
Magdeburg, Magdeburg
Purpose: In a previous study, the spectrum of mental disorders of long-
term cancer(Ca) survivors (LCS; time since initial diagnosis, 5 years[yr]
as minimum) and patients with acute Ca pain (acpp; initial diagnosis, 1-2
yr ago) was compared. ere were dierences in the total number of men-
tal disorders (LCS: 65.6%; acpp: 53.8%) as well as, among them, organic
mental disorders (9.8% vs. 2.2%) and addictions (13.1% vs. 2.2%). Ca of
the urogenital tract (uro-Ca) were more frequent in LCS and gastrointes-
tinal(GI) Ca in acpp. Since uro-Ca in general has usually a longer survival
time, the question arose whether the dierent prevalences are a function
of the duration.
Hypothesis: If the dierent numbers were a consequence of the type of
Ca, this distribution would also be apparent in acpp of the urogenital tract.
Methods: acpp” of the GI and urogenital tract were compared. e occur-
rence and distribution of mental disorders (F1-F4 according to ICD-10,
as well as psychologically normal ones) were investigated.
Results: Within the same period of time since initial diagnosis (GI=1.10
yr, Uro=1.37 yr), 50% of the GI patients had abnormal psychological nd-
ings, however, only 38.2% of the uro-patients. Addictions were found in
only 2.3% of uro Ca patients (ucp). Organic mental disorders were found
in 11.6% of ucp.
Conclusions: e acute ucp had less psychological disorders than the
acute GI-patients and, in particular, than LCS. is also applies to ad-
dictions. Derived from this, it can be assumed that mental disorders as a
specic group of patients as well as the individual diagnosis of addiction
develop to higher proportions over time.
is is in contrast to organic mental disorders, which already occur
as oen in acute ucp as in LCS. Here, the inuence of Ca diagnosis must
be assumed.
Disclosure Statement: Patients with a long history of Ca need to be examined for
the spectrum of various mental disorders, especially for addiction.
428
How Do Cancer Patients Experience Molecular Diagnostics?
Theresia Pichler 1, 2; Amy Rohrmoser 3; Anne Letsch 3, 4;
Benedikt Westphalen 1, 5; Ulrich Keilholz 3; Volker Heinemann 1, 5;
Peter Herschbach 1, 6; Ute Goerling 3
1Comprehensive Cancer Center München, München, Deutschland
2Klinikum rechts der Isar der Technischen Universität München, München,
Deutschland
3Charité – Universitätsmedizin Berlin, Charité Comprehensive Cancer Center,
Berlin, Deutschland
4Charité – Universitätsmedizin Berlin, Medizinische Klinik für Hämatologie und
Onkologie, Campus Benjamin Franklin, Berlin, Deutschland
5Klinikum der Universität München, Medizinische Klinik und Poliklinik III,
München, Deutschland
6Klinikum rechts der Isar der Technischen Universität München, Klinik und
Poliklinik für Psychosomatische Medizin und Psychotherapie, München,
Deutschland
Purpose: Research ndings within molecular diagnostic (MD) raise
hope for new eective cancer treatments. At the same time, evidence of
a treatment benet of MD is still limited for many malignancies. How-
ever, patients may hold high expectations nonetheless. To support these
patients suciently, deeper insight into their individual experience with
MD is needed. us, this study examines cancer patients’ perceived level
of information and expectations regarding MD.
Methods: In two German Comprehensive Cancer Centers, 30 cancer
patients undergoing MD participated in semi-structured interviews on
their subjective level of information and expectations regarding their MD
participation. Additionally, socio-demographic, medical, and distress data
was collected.
Results: While most patients understood their programs procedures,
many found the background of tumor genomic proling to be too com-
plex. In the tension between limited understanding and uncertainty about
a personal benet, they emphasized the importance of trusting their
doctor. Overall, patients mentioned three expectations of participating
in MD: 1) improving their treatment, 2) contributing to research and 3)
learning more about their tumor. Moreover, they described feeling indi-
vidually appreciated and maintaining hope for recovery by participating
in the MD program.
Conclusions: e results underline the signicance of the relationship
between patients and their oncologist within MD: Trusting their treating
physician can buer incomprehensible or missing information as well as
the uncertainty whether they will benet from MD at all. Also, patients
felt they were treated in a more “personalized” way. To balance patient
hopes and potential outcomes, oncologists and psycho-oncologists should
regularly and openly discuss treatment expectations as well as realistic
goals with their patients, thereby providing support and enabling an indi-
vidual and truly “personalized” treatment.
Disclosure Statement: e authors have nothing to disclose.
431
Distress in Patients with Non-Melanoma Skin Cancer
Caren Schierling 1; Andrea Forschner 2; Hans-Martin Häfner 2;
Stephan Zipfel 1; Andreas Stengel 1; Norbert Schäeler 1
1Universitätsklinikum Tübingen, Psychosomatische Medizin und
Psychotherapie, Tübingen, Deutschland
2Universitätsklinikum Tübingen, Universitäts-Hautklinik, Tübingen, Deutschland
Purpose: Non-Melanoma Skin Cancer (NMSC) is oen not regarded as
cancer by patients and considered less dangerous than malignant melano-
ma. Usually NMSC is treated curatively by surgical excision of the aected
area. So far, there is no reliable study examining the NMSC patients dis-
tress. e aim of this study was to examine the patients distress during the
oen several tumor surgeries to reach R0 resection.
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Methods: From 1/2018 to 2/2019 we examined N=168 inpatients at
the university skin clinic Tuebingen. To evaluate the distress, we used
Hornheider Screening Instrument (HSI), Patient-Health-Questionnaire
(PHQ-2), General Anxiety Disorder Screening (GAD-2), Distress er-
mometer (DT) and subjective need for support. Besides we used BFI-K
personality variables (based on the Big Five model) as possible predictors
and a self-developed questionnaire to investigate the patients awareness
of the disease. A diagnostic interview (based on QLQ-C30) and somatic
data from the clinical history completed the data collection. Follow-up
6 months aer the hospital-stay queried data on any changes of distress.
Results: Mean patient age was 62.9 years, 47.6% were female. e histo-
logically conrmed tumor type was in 79% (n1=133) basal cell carcinoma
and in 17% (n2=28) squamous cell carcinoma. In 68.4% tumor localiza-
tion was the facial area. e mean size of the largest operated defect was
5.5 cm². Patients with NMSC reported extremely low subjective support
needs (0.6%). Still, we identied an above-threshold value of DT in 46.1%.
In HSI 31.8% showed abnormal stress values, 11.7% indicated an anxiety
disorder (GAD-2) and 4.9% indicated depression (PHQ-2). Worries, anx-
ieties and sleep were most frequently mentioned in DT problem list.
Conclusions: Our data show that patients hardly express any subjective
need for psycho-oncological support, although a remarkable amount of
patients has increased distress levels. is could be due to the subjectively
lower threat attributed to NMSC. e follow-up was completed in 8/2019,
so that further results will be available at the congress.
566
Patientenkompetenz bei Krebspatienten: Welche Wirkung
haben Zeit seit Diagnose und eine kurative vs. palliative
Behandlungssituation?
Juergen M. Giesler 1; Joachim Weis 2
1Sektion Versorgungsforschung und Rehabilitationsforschung,
Universitätsklinikum Freiburg, Freiburg, Deutschland
2Stiftungsprofessur Selbsthilfeforschung, Tumorzentrum/CCC Freiburg,
Universitätsklinikum Freiburg, Freiburg, Deutschland
Purpose: Germany’s National Cancer Plan designates promoting Patient
Competence (PC) as one of its goals, while acknowledging a considerable
need of clarifying this concept itself and identifying potential determi-
nants and health-related outcomes. Against this background, we explored
potential eects of time since diagnosis (TSD) and a palliative treatment
situation on PC, coping self-ecacy, and quality of life.
Methods: In a study with three measurement points, we included 424
patients with breast, colorectal or prostate cancer in either oncological
rehabilitation or out-patient treatment (mean age 62 years, 53% female, 34%
under palliative treatment, median TSD 9.8 months). At each time point,
PC was measured with the Patient Competence Questionnaire 57 (PCQ-57)
that covers 8 PCs.1 To test for eects of TSD and treatment situation, we
computed 2 (TSD below median vs. TSD above median) x 2 (curative
vs. palliative treatment situation) ANOVAs on PC, coping self-ecacy
(CBI-B) and quality of life (QLQ-C30) as measured at baseline.
Results: Longer TSD was associated with signicantly stronger
competencies for seeking information, striving for autonomous decisions,
and using social benets, and also with better role functioning. Compared
to patients under curative treatment, patients under palliative treatment
reported dealing explicitly with the life-threat posed by cancer to a
signicantly larger extent. Also, they reported signicantly lower coping
self-ecacy and physical functioning. Eect sizes were generally small,
however.
Conclusions: e ndings suggest that a longer TSD and a palliative sit-
uation may independently impact on PC, coping self-ecacy and quality
of life. ey thus underline the need for supporting patients under these
conditions in their striving for autonomy and their coping eorts.
Reference:
1. Giesler JM, Weis J. Developing a self-rating measure of patient compe-
tence in the context of oncology: a multi-center study. Psychooncology.
2008;17(11):1089-1099.
Disclosure Statement: e authors have no conict of interest.
666
EPOS: Development and Evaluation of an Emotion-Based
Psychosocial Online Self-Help Program for Cancer Patients
Anna Mayer; Angeliki Tsiouris; Jörg Wiltink; Manfred E. Beutel;
Rüdiger Zwerenz
Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,
Universitätsmedizin Mainz, Mainz, Deutschland
Purpose: A cancer diagnosis is associated with considerable psychosocial
burdens and losses in quality of life. Many patients have problems to nd ad-
equate outpatient psycho-oncological help aer discharge from the clinic. In-
ternet-based interventions are regarded as a promising opportunity for can-
cer patients to overcome existing barriers to the use of psychosocial support
and to improve their psychological well-being, regardless of time or place.
Methods: Based on extensive literature research, focus groups with health
care professionals and interviews with cancer patients, we developed the
8-week online intervention epos (emotion-based psycho-oncological on-
line self-help). e program was designed for patients with all types of
cancer and follows the theoretical concepts of emotional mindfulness, re-
silience and positive psychology. It aims to reduce psychological distress
by (1) providing orientation and information (2) promoting their social
relationships and (3) strengthening their resilience.
Results: Epos includes an introductory module on mindfulness, followed
by seven modules on a specic psychosocial issue (e.g. talking about can-
cer, dealing with mental complaints, dealing with cancer in the social con-
text). Each module consists of psycho-educative elements as well as emo-
tion- or mindfulness-based exercises. Videos of ctional cancer patients
and psycho-oncological experts guide through the program.
Conclusions: With epos, an emotion-based online intervention has been
developed that complements conventional psycho-oncological treatment.
We assume that epos helps cancer patients to better cope with the major
psychological, social and physical challenges of the disease. In a random-
ized controlled trial (online self-help program + treatment as usual vs.
only treatment as usual) enrolling N=325 cancer patients, the ecacy and
acceptance of epos will be investigated.
Disclosure Statement: e authors declare no conict of interest.
695
Work Ability of Employed Cancer Survivors
Antonia Rabe 1; Elisabeth Jentschke 1; Tanja Bipp 2
1Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,
Würzburg, Deutschland
2Julius-Maximilians-Universität, Lehrstuhl für Psychologie II/ Arbeits-, Betriebs-
und Organisationspsychologie, Würzburg, Deutschland
Purpose: e aim of the study was to analyze work ability and its rela-
tionship with possible determinants, in particular with fatigue, occupa-
tional self-ecacy and job craing. It was examined, if self-ecacy and
job craing are helpful strategies to cope with fatigue at work and sustain
work ability.
Methods: A cross-sectional sample of individuals diagnosed with cancer
who nished primary treatment and have continued work lled out an
online questionnaire. Variables were assessed with common self-report
questionnaires. For consideration of the target group, a shortened version
of the Work Ability Index was used. Multiple regressions were executed
to examine associations while controlling for gender (female), working
hours and time since continuation of work. Additionally, participants
were asked which symptom was most hindering aer return to work.
Results: Participants (N = 69, female = 91.3%) were mostly diagnosed with
breast cancer (68.1%) and have reassumed work more than three years ago.
Fatigue was most frequently mentioned as a barrier aer return to work.
It was inverse related to general, physical and mental work ability. Women
and participants with a greater workload evaluated their work ability higher.
Moreover, participants with Fatigue reported a lower self-ecacy, but more
job craing. Job craing and self-ecacy did not moderate the relationship
between fatigue and work ability nor did job craing mediate it (p >.05).
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2018
Conclusions: Quantitative and qualitative ndings implicate the burden
of fatigue at work. Employed cancer survivors suering from fatigue are
at risk to rate their work ability lower. Special attention should be directed
to mental work ability. e relevance of self-ecacy and job craing for
work ability should be investigated in larger studies.
Disclosure Statement: No conict of interest or nancial ties.
699
Distress Experiences and Acceptance of a Computer Based
Screening in Neuro-Oncological Patients
Jan Ilgen 1; Mirjam Renovanz 2; Stephan Zipfel 1; Andreas Stengel 1;
Norbert Schäeler 1
1Universitätsklinikum Tübingen, Abteilung für Psychosomatische Medizin und
Psychotherapie, Tübingen, Deutschland
2Universitätsklinikum Tübingen, Abteilung für Neurochirurgie, Tübingen,
Deutschland
Purpose: Psycho-oncological screening is mandatory for patient-cen-
tered care in oncology. is is challenging in neuro-oncology as motor
and mental dysfunctions are common.
From 2/2018 to 2/2019 we examined n = 100 patients who were in the
neurosurgical department of the University Hospital Tübingen for surgi-
cal tumor therapy. e aim of the study is to investigate the patients dis-
tress experiences as well as their individual stress factors and the feasibility
of a computer-based screening.
Methods: e Electronic Psycho-oncological Screening (ePOS) was used
to assess patient’s distress. It includes the Hornheider Screening Instru-
ment (HSI), Patient Health Questionnaire (PHQ-4), Distress ermome-
ter (DT) and a question assessing the subjective need for support. e Re-
siliency Scale (RS-13), the Helping Alliance Questionnaire (HAQ-S) and
the Barthel Index as an clinician reported outcome, were also surveyed.
Patients were assessed postoperatively by using a tablet. A follow-up mea-
surement is scheduled 6 months aer the rst measurement date and will
be completed by 9/2019.
Results: e average patient age was 52 years (SD:14). 53% of the patients
were female. Subjective need for psycho-oncological support was reported
by 21% of the patients. In DT 65% showed increased values. In the HSI,
34% had a need for psycho-oncological treatment. Indications of an anx-
iety disorder were found in 24% and depression in 19%. In RS-13 87%
showed moderate to high values. About 80% indicated the family doctor
as their outpatient primary care provider. Overall, 74% were able to han-
dle the tablet on their own.
Conclusions: Our data show that about every h neuro-oncological pa-
tient indicates a subjective need for psycho-oncological support. Outpa-
tient family doctors play the most important role in primary care. Overall,
there is a high acceptance of the electronic screening in the perioperative
situation.
741
The Need for Psycho-Oncological Support in Colorectal Cancer
Patients during dierent Treatment Phases
Ralf Reichelt
Onkotrakt AG, Hamburg, Deutschland
Purpose: Colorectal cancer is frequently associated with psychooncolog-
ical burden for the aected patients. Severity and temporal dimension are
oen not readily assessable.e aim of this study was to identify patients
in need of psychooncological support and to monitor these patients in the
long-term.
Methods: e present study was conducted in 25 German hospitals. 604
colorectal cancer patients were asked to answer the self-assessment Ques-
tionnaire on Stress in Cancer Patients – short form (Herschbach & Weis,
2010) [1] at least twice throughout the observation period.
Results: Among all colorectal cancer patients included, 35,6% suered
from psychooncological distress at the time of the rst survey. ere was
no signicant dierence between women (39,3%) and men (33,3%). e
average lead time between the rst and the second survey was 33,4 weeks.
94 patients completed at least the 2nd survey. During the second survey,
39,3% of the 28 initially burdened patients were still identied to require
psychooncological support. Among the 66 (70,2%) initially burden-free
patients, 78,8% still showed no psychooncological distress at the time
of the second survey. However, fourteen individuals out of this group
(21,2%) exhibited signicant signs of psychooncological impairment.
Conclusions: Psychooncological burden was observed in 35,6% of the
colorectal cancer patients at an early stage during the course of the dis-
ease and during the second survey in approximately 20% of all patients
who initially did not show any signs of psychological impairment. is
argues in favor that psychooncological burden may well occur in a small
but signicant subset of initially unaected colorectal cancer patients aer
a prolonged period of time.
Reference:
1. Herschbach, P., Weis, J. (Hrsg.) (2010). Screeningverfahren in der Psychoonko-
logie Testinstrumente zur Identikation betreuungsbedüriger Krebspatienten.
Eine Empfehlung der PSO für die psychoonkologische Behandlungspraxis,
Berlin 2010, 2. Auage
Disclosure Statement: ere is no conict of interest.
789
Inuence of a Rehabilitative Treatment after Resection of a
Benign Meningioma
Katharina Krause 1; Almuth F. Keßler 2; Ralf-Ingo Ernestus 2; Mario Löhr 2;
Elisabeth Jentschke 1, 3
1Universitätsklinikum Würzburg, Neurochirurgie, Neuropsychologie, Würzburg,
Deutschland
2Universitätsklinikum Würzburg, Neurochirurgie, Würzburg, Deutschland
3Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,
Psychoonkologie, Würzburg, Deutschland
Purpose: e BReMen Study (Belastung und Rehabilitation bei Meningeom-
patienten) concentrates on the (neuro)psychological burdens and limitations
of patients with benign meningiomas and examines which inuence a reha-
bilitation has and whether there is an indicator of when rehab is necessary.
Methods: In a prospective longitudinal trial, 80 patients with benign menin-
giomas will be examined over a period of 2 years. Test time points included
pre- (T1), post-surgery (T2), 3, 6, 12 and 24 months post-surgery.
In addition to sociodemographic data, localization/size of the menin-
gioma, use of rehabilitation and its duration, time of reintegration will be
recorded.
Questionnaires used to assess quality of life and aect: Short-Form
Health Questionnaire (SF-36), EORTC Quality of Life Questionnaire - C30,
EORTC QLQ for brain tumor patients, PHQ-9 depression score, GAD-7
general anxiety score and distress thermometer.
Neuropsychological tests used to examine cognitive functioning: Verbal-
er Lern- und Merkfähigkeitstest, Wechsler Memory Scale Revised, Regens-
burger Wortüssigkeitstest, Trail Making Test A+B, Stroop-Test and d2-R
Aufmerksamkeits- und Belastungstest.
Results: is interim analysis focused on PHQ-9, GAD-7 and distress levels.
So far, 61 patients were recruited, 23 dropped out. From 38 patients
which were examined one year post-surgery 80% claimed rehab.
While both groups show increased distress values, patients receiving re-
hab show an earlier distress decrease with lower long-term values.
Patients with higher depressiveness and anxiety have a stronger desire
for rehab; a medium-term drop of these values can be observed, followed by
a renewed increase to T5.
Conclusions: Increased depressiveness levels appear to be an indicator of
rehab need.
e stronger reduction of distress, depressivity and anxiety in the rehab
group indicate a positive rehab eect, while the later increase in depres-
siveness and anxiety levels seems to mark the need for further (neuro)
psychological care.
Disclosure Statement: No conicts of interest or nancial ties.
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842
A Clinical Trial of Group-Based Body Psychotherapy
to Improve Bodily Disturbances in Cancer Patients in
Combination with Randomized Controlled Smartphone-
Triggered Bodily Interventions – First Results
Astrid Grossert-Leugger 1, 2; Cornelia Meert 1; Viviane Hess 2, 3;
Christoph Rochlitz 2, 3; Miklos Pless 4; Sabina Hunziker 1, 3; Brigitta
Woessmer 5; Ulfried Geuter 6; Gunther Meinlschmidt 1, 3, 7, 8; Rainer Schäfert 1, 3
1Department of Psychosomatic Medicine, University Hospital Basel, Basel,
Schweiz
2Department of Medical Oncology, University Hospital Basel, Basel, Schweiz
3Faculty of Medicine, University of Basel, Basel, Schweiz
4Department of Medical Oncology, Winterthur Cantonal Hospital, Schweiz
5Outpatient practice for psychotherapy, Olten, Schweiz
6Institute for Sports and Motology, University of Marburg, Marburg, Schweiz
7Division of Clinical Psychology and Epidemiology Department of Psychology,
University of Basel, Basel, Schweiz
8Division of Clinical Psychology and Cognitive Behavioral Therapy , International
Psychoanalytic University, Berlin, Deutschland
Purpose: Disturbances in bodily well-being represent one key source of
suering and impairment related to cancer. ere is growing evidence that
body psychotherapy (BPT) is ecacious for the treatment of various men-
tal health problems. However, with regard to cancer patients, evidence is
scarce. Our aim was to evaluate whether group BPT can improve bodily
disturbances in post-treatment cancer patients.
Methods: Pre-post convergent parallel design of group BPT (6 weekly
sessions) using a waiting-period comparator, including a nested RCT:
During the BPT phase, either a smartphone-triggered bodily interven-
tion or a smartphone-triggered control intervention is provided at ran-
dom over 5 consecutive weeks, on 6 days weekly. Assessment took place at
three times (baseline, pre- and post-intervention), and on a daily basis for
the smartphone-triggered interventions. Inclusion criteria: Patients who
had received curatively intended treatment for any malignant neoplasm
(treatment being completed ≥3 months) and were suering from bodily
disturbances. Primary outcome: bodily disturbances assessed using the
‘Body Image Scale. For the secondary outcomes standardized question-
naires are used to assess changes in experience of presence and vitality,
mood, body mindfulness, somatic symptoms and somatic symptom dis-
order, quality of life, anxiety, and depression including suicidal tendency,
vitality and mental health, as well as group cohesion.
Results: 171 patients were screened for eligibility; 40 patients attended the
group BPT and were randomized on a daily basis. 7 groups were conduct-
ed. Median age was 51.7 (22-77)y. 35 (87.5%) were female. 23 (57.5%) had
a malignant neoplasma of breast, 7 (17.5%) a lymphoma, 10 (25%) were
spread over various cancer types. Data analysis is ongoing at the time of
submission. First results will be presented at DKK.
Conclusions: Our trial has strong potential benets for cancer patients, as
it may introduce new therapeutic approaches to treat bodily disturbance
that persist despite curative tumor therapy.
Quality of Life
Poster
106
The Relationship between Posttraumatic Growth and Health-
Related Quality of Life in Adult Cancer Survivors: A Systematic
Review
Zhunzhun Liu; Daniela Doege; Melissa Thong; Volker Arndt
German Cancer Research Center (DKFZ), Unit of Cancer Survivorship, Division of
Clinical Epidemiology and Aging Research, Heidelberg, Deutschland
Purpose: Studies reported dierent results on the relationship between
posttraumatic growth (PTG) and health-related quality of life (HRQOL)
in cancer survivors. is review aims to give an overview of current stud-
ies and to identify factors that potentially contribute to the heterogeneity
of the results on this topic.
Methods: is systematic review was registered in the International Pro-
spective Register of Systematic Reviews (ID: CRD42019121828), and con-
ducted and reported in accordance with PRISMA (Preferred Reporting
Items for Systematic Reviews and Meta-Analyses) guidelines. Eight litera-
ture databases were systematically searched using the concepts ‘posttrau-
matic growth, ‘cancer’, and ‘health-related quality of life. Eligible studies
(published until 2018) were reviewed, quality-assessed, and eect sizes
were extracted and synthesized.
Results: Of the 37 included articles, 22 received a rating of ‘weak, 11 ‘mod-
erate’ and 4 ‘strong’ in study quality assessment. irty-ve independent
samples, mainly assessed in cross-sectional studies, were identied. e
overall sample comprised 7954 individuals, mean age of 55.3 years, >50%
females, predominantly breast cancer, and mainly focused on short-term
survivors (<5 years post-diagnosis). Variations in HRQOL measurement
and methodological inconsistency contributed to study-level dierences
of eect sizes. Sample-level factors were gender, cancer diagnosis, mean
age at study and geographic origin. Excluding studies of prostate cancer
survivors led to a decrease in heterogeneity regarding gender and diag-
nosis.
Conclusions: Studies assessing the relationship between PTG and
HRQOL were heterogeneous and results were dicult to combine. Over-
all, most studies found a positive relationship between the factors. How-
ever, studies of higher quality and longitudinal design are needed to better
understand the mechanisms behind that relationship, and to determine
whether PTG in cancer survivors can be modied by intervention in order
to improve HRQOL.
Disclosure Statement: None.
125
HELP (Heidelberger Entscheidungshilfen für Lungenkrebs-
Patienten) – Decision Aids for Lung Cancer Patients
Laura Unsöld; Nicole Deis; Anja Siegle; Corinna Jung;
Matthias Villalobos; Michael Thomas
Thoraxklinik Heidelberg, Onkologie der Thoraxtumoren, Heidelberg,
Deutschland
Purpose: Preference for patient participation increased over the past
30 years. Especially cancer patients with a limited prognosis have a strong
wish for information and participation. Decision aids (DA) are useful in-
strument to meet these needs. ey increase patients’ knowledge regard-
ing options and reduce decisional conicts. Benets of DA, relative to
usual care, are better knowledge of options, outcomes and more accurate
perceptions of outcome probabilities. Nonetheless, the use of DA by on-
cologists is still highly improvable. In the setting of limited prognosis that
comprises not only physical and psychosocial burden but also confronts
the patients and their relatives with an existential threat, many possible
barriers may hinder the adequate use of standardized aids. erefore the
aim of our project is the qualitative exploration, development and success-
ful implementation of DA for lung cancer patients.
Methods: 25 structured interviews with patients and their relatives will
be conducted regarding their wishes, needs and ideas in the decision
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making process. e healthcare-professionals perspective will be collected
through focus groups and all data will be analyzed with content analysis.
Based on these results and a thorough literature search, DA will be
developed and tested with the help of patient representatives. Aer a trial
period, the DA will be implemented in daily clinical practice following an
implementation plan. e success of the implementation will be measured
in the dimensions adherence and acceptance.
Results: Mainly focusing on the development of patient oriented DA and
their implementation rst preliminary results will be available up to the
time of the congress.
Conclusions: rough the integration of DA in clinical practice patients
and their family care-givers can be more actively involved in therapy- de-
cisions and patient’s competency and autonomy will be enhanced. e
implementation in daily clinical practice will be particularly challenging
as it also implicates dealing with important barriers perceived by the pro-
fessionals.
138
Prevalence and Intensity of Cancer-Related Fatigue Across a
Variety of Cancer Entities
Martina Schmidt 1; Silke Hermann 2; Karen Steindorf 1
1Division of Physical Activity, Prevention and Cancer, German Cancer Research
Center (DKFZ), Heidelberg, Deutschland
2Epidemiological Cancer Registry , German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
Purpose: To systematically assess and compare prevalence and intensity
of fatigue across the 16 most frequent cancer entities.
Methods: e FiX study enrolled cancer patients 1-2 years aer diagnosis
via the Epidemiological Cancer Registry of Baden-Württemberg. Fatigue
was assessed with the multidimensional EORTC QLQ-FA12 question-
naire. Age, sex, tumor and treatment data were derived from the cancer
registry. For calculating prevalence, patients with scores higher than the
age- and gender-specic 75th percentile from a representative sample of
the German general population were considered fatigued [1].
Results: A total of n=2,256 patients (50% male, 5% metastasized) with
a mean age of 66 ± 12 years were included in this analysis. e medi-
an (Q1, Q3) raw scores of physical fatigue ranged from 26.7 (13.3, 53.3)
among prostate and 33.3 (16.7, 66.7) among breast to 46.7 (26.7, 66.7) and
46.7 (26.7, 73.3) among stomach and pancreas cancer patients, respec-
tively. Prevalence was calculated for all fatigue dimensions and entities.
For example, physical fatigue was prevalent in 34% of prostate and 54%
of lung cancer patients. Aer adjusting for determinants of fatigue, i.e.
sex, age, BMI, type and timing of therapy, the intensity of physical fatigue
still diered among tumor entities (p = 0.018) with highest values among
patients with stomach, lung, pancreas, and kidney cancer and lowest val-
ues among patients with prostate and breast cancer. Breast cancer patients
also showed lowest adjusted levels of emotional fatigue.
Conclusions: Fatigue occurs across a large variety of cancer entities. In-
tensity and prevalence of fatigue in breast and prostate cancer patients
were in the lowest range among the 16 entities studied. As the majority
of observational and interventional research on fatigue is based on breast
cancer patients, the scope of this burdensome problem is probably not
fully ascertained.
Reference:
1. Hinz A, Weis J, Brähler E, Mehnert A. Fatigue in the general population:
German normative values of the EORTC QLQ-FA12. Qual Life Res.
2018;27:2681-2689
Disclosure Statement: none
226
Top 10 Living with and Beyond Cancer Research Priorities
Feng LI 1; Mariano Kalfors 1; Alexander Renziehausen 1; Patricia Ellis 2;
Stuart Griths 1; Ian Lewis 1; Ncri Lwbc Steering Group 3
1National Cancer Research Institute, London, United Kingdom
2James Lind Alliance, Southampton, United Kingdom
3https://www.ncri.org.uk/lwbc/about-psp/steering-group-and-partners/
Purpose: Currently 2.5 million people in the United Kingdom (UK) live
with a diagnosis of cancer and it is projected that by 2030 it will be over
four million [1]. Despite this, investment in research that aims to help
people live better with and beyond a cancer diagnosis has remained con-
sistently low and is currently only around 6% of UK cancer research spend
[3]. To address this, the 2015 National Health Service (NHS) England’s
Independent Cancer Taskforce report recommended identifying research
priorities on long-term patient needs and survivorship issues. Subse-
quently, the National Cancer Research Institute (NCRI), a partnership
of major cancer research funders, formed a Priority Setting Partnership
(PSP) with the James Lind Alliance to develop a list of priorities for Living
With and Beyond Cancer (LWBC) research.
Methods: e PSP had several stages, beginning with a UK-wide survey
to gather questions about uncertainties in living with and beyond cancer.
ese were further prioritized through an interim analysis and a second
survey before the top 10 list was decided during a nal stakeholder work-
shop. PSP participation was open to any adult rst diagnosed with can-
cer over the age of 16, their carers and health & social care professionals.
Questions on new cancer treatments solely aimed at extending life or only
relevant to end of life care were excluded.
Results: e rst survey had 1492 respondents who proposed 3500 unan-
swered questions and through an 18-month established rigorous process,
the questions were prioritized down to the Top 10 LWBC research priori-
ties (www.ncri.org.uk/lwbc).
Conclusions: is is the rst time that clear research priorities have been
identied in the UK to address questions that matter most to people af-
fected by cancer. e NCRI is working with funders, researchers, the NHS
and others to translate the priorities into research and patient benet, as
well as raise awareness of them internationally.
References:
1. Maddams J et al. (2012) BJC;107:1195–1202.
2. NCRI Cancer Research Database [Online, last accessed 18 March 2019].
Disclosure Statement: None
249
Impact Of Darolutamide (DARO) On Pain and Quality of Life
(QoL) in Patients (PTS) with Nonmetastatic Castrate-Resistant
Prostate Cancer (NMCRPC)
Tilman Todenhöfer 1; Karim Fizazi 2; Neal D. Shore 3; Teuvo Tammela 4;
Iris Kuss 5; Marie-Aude Le Berre 5; Ateesha F. Mohamed 5; Dawn Odom 6;
Jennifer Bartsch 6; Amir Snapir 7; Toni Sarapohja 7;
Matthew Raymond Smith 8
1Studienpraxis Urologie, Nürtingen, Deutschland
2Institute Gusta, University of Paris Sud, Villejuif, Frankreich
3Carolina Urologic Research Center, Myrtle Beach
4Department of Surgery, Tampere University Hospital, Tampere, Finnland
5Bayer AG, Berlin, Deutschland
6Research Triangle Institute, Durham, United States
7Orion Pharma, Orion Corporation, Espoo, Finnland
8Massachusetts General Hospital, Medicine, Boston, United States
Purpose: DARO is a structurally distinct androgen receptor antagonist
for which in vitro and phase 1/2 studies suggest low risk of adverse events
(AEs) and drug–drug interaction. In the ARAMIS study of DARO in
nmCRPC, metastasis-free survival (MFS) was signicantly prolonged vs
placebo (PBO) (40.4 vs 18.4 mo; hazard ratio [HR] 0.41; 95% condence
interval [CI] 0.34–0.50; P < 0.001) and interim overall survival (OS)
favored DARO (HR 0.71; 95% CI 0.50–0.99; P = 0.045).
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Methods: 1509 pts were randomized 2:1 to DARO 600 mg (two 300 mg
tablets) twice daily (n = 955) or PBO (n = 554) while continuing androgen
deprivation therapy (ADT). Primary endpoint was MFS. Secondary
endpoints included OS and time to pain progression. QoL was assessed
by EORTC-QLQ-PR25 at baseline (BL) and every 16 wks until end of
treatment. Analysis of time to deterioration (TTD) in EORTC-QLQ-PR25
subscales, dened as rst occurrence of a minimally important dierence.
Results: DARO signicantly delayed pain progression vs PBO (40.3 vs
25.4 mo; HR 0.65; 95% CI 0.53–0.79; P < 0.001); this was maintained be-
yond end of study treatment. TTD showed statistically and clinically sig-
nicant delays with DARO vs PBO for urinary symptoms (25.8 vs 14.8 mo;
HR 0.64; 95% CI 0.54–0.76; P < 0.01). TTD of hormonal treatment-related
symptoms was comparable with DARO vs PBO (18.9 vs 18.4 mo; HR 1.06;
95% CI 0.88–1.27; P = 0.52). DARO was well tolerated. Exposure-adjust-
ed incidences of AEs of interest were similar/lower with DARO vs PBO
(fatigue/asthenic conditions [11.3 vs 11.1], hypertension [4.7 vs 5.1], hot
ush [3.7 vs 4.1], fracture [3.0 vs 3.5], falls [2.7 vs 4.1], cognitive disorder
[0.3 vs 0.2], and seizure [0.2 vs 0.2]).
Conclusions: For nmCRPC pts, DARO prolongs MFS, is well tolerated,
maintains QoL, and delays worsening of pain and disease-related symp-
toms compared with PBO.
Disclosure Statement: Clinical trial information: NCT02200614. © 2019
American Society of Clinical Oncology; Inc. Reused with permission. is abstract
was accepted and previously presented at the 2019 ASCO Annual Meeting. All
rights reserved.
Tilman Todenhöfer reports personal fees from Bayer Healthcare, Janssen, Astellas
outside the submitted work.
Karim Fizazi reports personal fees from Amgen, Astellas, Bayer, Clovis,
AstraZeneca, Janssen, Curevac, ESSA, Orion Pharma, Roche/Genentech, and
Sano outside the submitted work.
Neal D. Shore reports personal fees from Ferring, Bayer, Amgen, Janssen,
Dendreon, Tolmar, Astellas, Pzer, AstraZeneca, Genentech/Roche, Myovant
Sciences, Merck, AstraZeneca, Bristol Meyers Squibb, and Nymox outside the
submitted work.
Teuvo Tammela reports personal fees from Janssen, grants and personal fees from
Bayer, Lidds AB and Astellas, outside the submitted work.
Iris Kuss reports employment by and stock ownership in Bayer
Marie-Aude Le Berre is an employee of Bayer.
Ateesha F. Mohamed is an employee of Bayer.
Dawn Odom is a full time salaried employee of RTI Health Solutions. RTI Health
Solutions was retained by Bayer to conduct the analysis which is the subject of this
abstract.
Jennifer Bartsch is a full time salaried employee of RTI Health Solutions. RTI
Health Solutions was retained by Bayer to conduct the analysis which is the subject
of this abstract.
Amir Snapir reports personal fees from Orion Pharma during the conduct of the
study.
Toni Sarapohja reports to be an employee of Orion Corporation.
Matthew Raymond Smith reports personal fees from Amgen, Astellas, Bayer,
Clovis, Gilead, Janssen, Lilly, Novartis, and Pzer, outside the submitted work.
281
Association of Laparoscopic Colectomy Versus Open
Colectomy on the Long-Term Health-Related Quality of Life of
Colon Cancer Survivors
Melissa Thong 1; Lina Jansen 2; Jenny Chang-Claude 3;
Michael Homeister 2; Hermann Brenner 2; Volker Arndt 1
1DKFZ, Unit of Cancer Survivorship, Heidelberg, Deutschland
2DKFZ, Division of Clinical Epidemiology and Aging Research, Heidelberg,
Deutschland
3DKFZ, Division of Cancer Epidemiology, Heidelberg, Deutschland
Purpose: Laparoscopic colectomy (LC) is promoted as a less invasive al-
ternative to open colectomy (OC) in the treatment of stage I-III colon
cancer. Research on the long-term (5-years post-diagnosis) health-related
quality of life (HRQOL) of LC patients is scarce. Our study aimed to com-
pare the long-term HRQOL and psychological well-being of stage I-III
colon cancer survivors treated either with LC or OC.
Methods: is study used a German population-based cohort of 1066 pa-
tients who underwent either LC (n=86) or OC (n=980). LC patients were
matched to OC patients with a propensity score using a 1:2 nearest-neigh-
bor algorithm. e propensity score is derived from a set of baseline so-
ciodemographic, clinical, and lifestyle covariates. At 5-year follow-up,
patients completed assessments on HRQOL (EORTC-QLQ-C30 and
EORTC-QLQ-CR29) and psychological well-being (distress and disease/
treatment burden). Least square mean scores of HRQOL were derived us-
ing linear regression. Proportions of patients with moderate/high distress
and disease/treatment burden versus low were compared with chi-square
tests.
Results: In total, 81 LC patients could be matched to 156 OC patients.
More LC patients experienced disease progression (16% versus 7%,
p=0.02). On HRQOL, LC patients reported signicantly better body im-
age (87.1 versus 81.0, p=0.03) and generally less symptom burden, albeit
dierences were not signicant. Distress levels were generally low and
comparable between the two groups. OC patients were more likely to feel
moderate/high levels of burden associated with the treatment (72% versus
56%, p=0.01) and the time aer treatment completion (43% versus 28%,
p=0.02).
Conclusions: LC was associated with higher risk of disease progression
among stage I-III CRC patients, but LC patients reported comparable or
better long-term HRQOL outcomes and higher levels of psychological
well-being than OC patients 5 years aer diagnosis.
Disclosure Statement: No conict of interest declared.
289
Depression in Long-Term Breast Cancer Survivors Compared
to Female Population Controls in Germany: Age-Specic
Prevalence and Determinants
Daniela Doege 1; Melissa Thong 1; Lena Koch-Gallenkamp 2; Lina Jansen 2;
Heike Bertram 3; Andrea Eberle 4; Bernd Holleczek 5; Ron Pritzkuleit 6;
Annika Waldmann 7, 8; Sylke Zeißig 9; Hermann Brenner 2, 10, 11; Volker Arndt 1
1German Cancer Research Center (DKFZ), Unit of Cancer Survivorship, Division
of Clinical Epidemiology and Aging Research, Heidelberg, Deutschland
2German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and
Aging Research, Heidelberg, Deutschland
3Cancer Registry of North Rhine-Westphalia, Bochum, Deutschland
4Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen
Cancer Registry, Bremen, Deutschland
5Saarland Cancer Registry, Saarbrücken, Deutschland
6Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland
7Ministry of Health and Consumer Protection, Hamburg Cancer Registry,
Hamburg, Deutschland
8University Lübeck, Institute of Social Medicine and Epidemiology, Lübeck,
Deutschland
9Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland
10German Cancer Research Center (DKFZ), Division of Preventive Oncology,
Heidelberg, Deutschland
11German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK),
Heidelberg, Deutschland
Purpose: Depression is more prevalent in breast cancer (BC) patients
and survivors than in general population. However, little is known about
depression in (very) long-term survivors. e study objectives were (1)
to compare the age-specic prevalence of depressive symptoms (a) in BC
survivors vs. female population controls, (b) in disease-free BC survivors
vs. those who self-reported progression aer treatment vs. controls, and
(2) to explore determinants of depression in BC survivors.
Methods: 3010 BC survivors (stage I-III, 5-16 years post-diagnosis, mean
age 65 years at survey), and 1005 cancer-free population controls (mean
age 59 years) were recruited in German multi-regional population-based
studies. Depression was assessed by the short form of the Geriatric De-
pression Scale (GDS-15). Prevalence dierences between subgroups were
assessed via logistic regression, controlling for age and education. Multi-
nomial logistic regression was used to explore determinants of depression
in BC survivors.
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Results: A GDS-15 score suggestive of mild or severe depression (cut-o:
≥5) was found in 30.4% of BC survivors and in 23.8% of cancer-free con-
trols (p<0.0001), and a score suggestive of severe depression (cut-o: ≥10)
in 4.7% of BC survivors and 3.8% of controls (p=0.2107). At all ages <80
years, prevalence of mild/severe depression was signicantly higher in BC
survivors than controls, while at ≥80 years BC survivors showed lower
rates of severe depression than controls. BC survivors with progression
showed signicantly higher prevalence of mild/severe depression than
disease-free survivors and controls. Age, employment, income, partner-
ship, living situation and BMI were signicant predictors of depression
in BC survivors.
Conclusions: Long-term BC survivors <80 years report slightly but sig-
nicantly higher depression prevalence than controls, which might be
explained by disease progression. Clinicians should refer survivors to psy-
chological care when needed, especially in the case of disease progression.
Disclosure Statement: No conict of interest.
311
Validation of the Cancer Fatigue Scale in a Geriatric
Population
Anne-Kathrin Klaus 1, 3, 4; Roland Zerm 1, 3; Anette Mehl 3;
Thomas Ostermann 2, 5; Daniela Rodrigues Recchia 5; Marcus Reif 6;
Hans Broder von Laue 3; Benno Brinkhaus 4; Matthias Kröz 1, 2, 3, 4
1Hospital Havelhöhe, Internal Medicine, Berlin, Deutschland
2Witten/ Herdecke University, Integrative Medicine, Witten, Deutschland
3Research Institute Havelhöhe, Berlin, Deutschland
4Charité University, Institute for Social Medicine, Epidemiology and Health
Economics, Berlin, Deutschland
5Witten/ Herdecke University, Methodology and Statistics in Psychology and
Psychotherapy, Witten, Deutschland
6Society for Clinical Research, Berlin, Deutschland
Purpose: Cancer related Fatigue (CRF) is a burdensome symptom both
generally and particularly in geriatric cancer patients. A variety of validat-
ed questionnaires exist to assess CRF, either unidimensional, e.g. Function-
al Assessment of Chronic Illness erapy-Fatigue or multidimensional,
e.g. Multidimensional Fatigue Inventory or the Cancer Fatigue Scale
(CFS-D). e CFS-D is validated in German for cancer patients from 30
to 83 years with robust validity. Since there is no validation specically
for a geriatric population older than 83 years we conducted this geriatric
validation study.
Methods: Reliability of the CFS-D has been assessed by Cronbach-α, and
test-retest reliability (with a test-retest time-span of 2–4 weeks) by Spear-
man rank correlation. Additionally, a factor analysis and a structural equal
modeling (SEM) has been conducted. e cumulative illness rating scale
(CIRS), physical self-maintenance scale (PSMS), geriatric depression scale
(GDS), sleep quality (DGSM), health-related quality of life (SF-12), Kar-
nofsky performance index (KPI) and actigraphy have been recorded as
external validity criteria.
Results: We included 104 participants between 70 and 96 years (31 cancer,
22 diabetes mellitus type 2, and 51 age-matched comparatively healthy
controls. e 15-item CFS-D questionnaire revealed good internal con-
sistency (Cronbachs-α r = 0.88) and satisfying test-retest reliability (r =
0.68). Concordant construct and convergent validity with correlations
to CIRS, PSMS, GDS, SF-12 and actigraphical rest/activity rhythm vari-
ability were documented (r = 0.28–0.49, all p<0.05). e factor analysis
revealed a 3-factor structure. Although the subscales diered in item load-
ing from the published CFS-D the SEM conrmed the initial validation
subscales structure (physical, cognitive, aective fatigue) to be robust and
usable for a geriatric sample.
Conclusions: e Cancer Fatigue Scale (CFS-D) is a reliable and valid
questionnaire to measure fatigue up to 96 years, however subscale dier-
ences demand clarication for highly aged individuals.
441
Inuencing Factors on the Development of Physical
Functioning of Older Cancer Patients During and 12 months
After Cancer Therapy - A Prospective Observational Study
Johannes Kooymann 1; Stephanie Witte 1; Daniel Medenwald 2;
André Golla 3; Gabriele Stangl 4; Anke Steckelberg 1; Dirk Vordermark 2;
Heike Schmidt 1
1Institute of Health and Nursing Science, Medical Faculty of Martin Luther
University Halle-Wittenberg, Halle (Saale), Deutschland
2University Clinic and Outpatient Clinic for Radiotherapy, Medical Faculty of
Martin Luther University Halle-Wittenberg, Halle
3Institute of Rehabilitation Medicine, Medical Faculty of Martin Luther
University Halle-Wittenberg, Halle
4Institute for Agricultural and Nutritional Science, Martin Luther University
Halle-Wittenberg, Halle
Purpose: is study aims to generate hypotheses regarding modiable
factors associated with the development of physical function of older can-
cer patients undergoing cancer therapy.
Methods: Exploratory, prospective observational study including cancer
patients ≥65 years treated with radiotherapy. Assessments of ADL, IADL,
physical function (TUG, handgrip, 6 min. walk test), physical activity
(PASE), nutritional status, cognition (minicog), depressed mood (PHQ9),
social situation and health-related quality of life (EORTC QLQ-C30,
ELD14) at baseline (t0), 6 (t2) and 12 months (t4); postal assessments at 3
(t1) and 9 months (t3). Descriptive analyses included Spearmans Rho (rs)
to examine associations between the EORTC QLQ-C30 subscale physical
function (PF) and possible inuencing factors.
Results: Forty patients, mean age 74.4 ±5.3 years, n=24 male, participated.
Analyses show a clinically relevant change of PF over time (Ø t0: 79.8 ±8.1;
Ø t1: 63.6 ±26.9; Ø t2: 65.0 ±26.7; t3: ø 60.8 ±25.7; t4: ø 61.7 ±34.0). Data
show correlations of albumin (t0) with PF (t2) (rs=0,446) and depressed
mood PHQ9 (t0) with decreased PF at t2 (t2: rs=-0,486). At 12 months
the correlation of PHQ9 (t4) with PF (t4) is stronger (t4: rs=-0.532) than
the correlation of the EORTC QLQ-C30 subscale emotional function with
PF (rs=0,526). Out of the objective assessments, baseline TUG shows the
strongest correlation with PF at t2 and t4 (t2: rs=-0.523; t4 rs=-0.605).
Conclusions: While 6 months data indicate that baseline mental health
and good nutritional status are associated with the maintenance of physi-
cal function, at 12 months mental health shows the strongest association.
Aiming for targeted interventions, these hypotheses should be examined
in further studies.
Disclosure Statement: e authors do not have any conicts of interest relevant to
the topic to declare.
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445
AML Survivorship – Somatic and Psychosocial Long-Term
Eects of AML Therapy
Eva Telzerow 1, 2; Maria Christina Sauerland 3; Maja Rothenberg-Thurley 2;
Friederike Mumm 2; Jan Braess 4; Bernhard Wörmann 5; Utz Krug 6;
Wolfgang E. Berdel 7; Michael von Bergwelt-Baildon 2;
Wolfgang Hiddemann 2; Karsten Spiekermann 2; Pia Heußner 2, 8;
Dennis Görlich 3; Klaus Metzeler 2
1Psycho-Oncology, Comprehensive Cancer Center, Ludwig-Maximilians-
University Munich, Munich, Deutschland
2Department of Internal Medicine III, Ludwig-Maximilians-University Munich,
Munich, Deutschland
3Institute of Biostatistics and Clinical Research, Westfälische Wilhelms-
Universität Münster, Münster, Deutschland
4Department of Oncology and Hematology, Hospital Barmherzige Brüder,
Regensburg, Deutschland
5Charité University Hospital Berlin, Berlin, Deutschland
6Hospital Leverkusen, Leverkusen, Deutschland
7Deparment of Medicine A, Westfälische Wilhelms-Universität Münster, Münster,
Deutschland
8Hospital Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland
Purpose: An increasing proportion of patients with Acute Myeloid Leu-
kemia (AML) become long-term survivors. Somatic and psycho-social
outcomes are therefore becoming increasingly important, but little is
known about the long-term eects of the disease and its treatment. We
therefore designed a comprehensive analysis of AML survivorship out-
comes on multiple levels: somatic health status, psycho-social well-be-
ing, and genetics (clonal hematopoiesis). ese data will aid in designing
risk-adapted follow-up programs for long-term survivors.
Methods: We are including adult AML patients who were enrolled in
AML-CG multicenter trials (AML-CG 1999, AML-CG 2004 and AML-
CG 2008) or in the AML-CG patient registry, and who are alive and in
remission ≥5 years aer their initial diagnosis. Eligible patients receive a
14-page questionnaire with standardized instruments addressing dierent
relevant aspects of survivorship, including quality of life, life satisfaction,
fatigue, somatic health status and socio-economic status. e results will
be compared to data from age-matched healthy adults to assess the impact
of past AML therapy on various domains of well-being.
In a second step, we are also asking patients to also provide a periph-
eral blood sample, aiming to study leukemia-associated or treatment-in-
duced genetic alterations in long-term survivors. We will use these genet-
ic data to study associations between treatment regimens (e.g. allogeneic
transplantation), clonal hematopoiesis, and relevant long-term health out-
comes such as cardiovascular disease.
Results: 820 eligible potential participants have been identied. In a fea-
sibility study, 102 of 200 persons (51%) responded to the rst invitation
to participate. Enrollment is ongoing, and we expect to obtain data from
approximately 400 former AML patients. First results on recruitment and
descriptive analysis of relevant aspects on survivorship will be presented
at the meeting.
Conclusions: We will present an ongoing study of long-term health out-
comes in AML survivors.
448
Health-Related Quality of Life (HRQOL) Reported by Patients
with Multiple Myeloma (MM) in Germany
Monika Engelhardt 1; Gabriele Ihorst 2; Moushmi Singh 3; Martina Schöhl 4;
Achim Rieth 4; Grece Saba 5; Marine Pellan 5; Andrea Lebioda 4
1University Hospital Freiburg, Klinik für Innere Medizin, Klinik für Tumorbiologie,
Freiburg, Deutschland
2University Medical Center Freiburg, Freiburg im Breisgau, Deutschland
3Amgen, Denham, United Kingdom
4AMGEN GmbH, München, Deutschland
5Kantar, Paris, Frankreich
Purpose: Patient-focused care is the key to optimal management of
multiple myeloma (MM). Novel treatment options have improved life
expectancy, but real-world data on health-related quality of life (HRQoL)
is still scarce. Here, we report HRQoL of patients with MM by number of
treatment lines in real-world clinical practice in Germany.
Methods: An observational, cross-sectional, multicenter study was con-
ducted in 2019 to assess overall QoL global health status (GHS), function-
al capacity, and symptoms using the validated European Organization for
Research and Treatment of Cancer (EORTC) Core Quality of Life ques-
tionnaire (QLQ-C30) and the Quality of Life Multiple Myeloma module
(QLQ-MY20). For bivariate analyses, Student´s t-tests or one-way anova
were used, while Pearson´s chi-squares were applied for categorical vari-
ables. For subgroup analyses multivariate analyses have been used. Miss-
ing values have been excluded from the analyses.
Results: In total, 490 myeloma patients from 40 German centers were en-
rolled. e care setting included oce-based practitioners (43%), cancer
centers (25%), hospitals (23%) and university hospitals (10%). Median age
of patients was 72 years and 62% were male. At study participation, 71%
of patients were actively treated. Over a third (35%) had a previous stem
cell transplantation. Most (77%) patients had ≥1 comorbidity. Mean (stan-
dard deviation [SD]) EORTC QLQ-C30 GHS scores decreased from 61.7
(19.3) in 1st line (n=101) to 46.3 (19.4) in 4th line (4L) or later (n=97). e
mean dierence in GHS scores was 6.4 between 2nd and 3rd line and was
the highest (15.3) between supportive care and 4L. In all functional and
symptom scales, HRQoL was worsening as the number of treatment lines
increased. Similar results were found using EORTC QLQ-MY20 scales.
Conclusions: e observed HRQoL deterioration in later versus earlier
lines, stresses the importance of maintaining HRQoL for as long as pos-
sible. As age, remission, comorbidities and therapy are interacting with
HRQoL, further HRQoL analyses are needed to determine how to pre-
serve QoL of MM patients.
Conicts of Interest:
M. Engelhardt: ME has received educational and trial support from Amgen,
Celgene, Takeda, BMS, Janssen, Novartis, Karyopharm, and has received honoraria
and consultancy fees from BMS, Celgene, Amgen, Takeda, Novartis and Janssen.
G. Ihorst has received consultancy fees from Amgen.
G. Saba and M. Pellan are employees of Kantar Health who received funding from
Amgen to conduct this research.
A. Rieth, M. Schoehl and A. Lebioda are employees of Amgen GmbH and hold
Amgen stocks.
M. Singh is an employee of Amgen Ltd. Uxbridge.
489
Development of Tumor Disease-Specic PRO-CTCAE Item Sets
Maximilian Günther 1; Markus Schuler 2; Leopold Hentschel 3;
Katharina Schütte 3; Yon-Dschun Ko 4; Ingo Schmidt-Wolf 5; Ulrich Jaehde 1
1Clinical Pharmacy, University of Bonn, Bonn, Deutschland
2Department of Oncology, Helios Hospital Emil von Behring, Berlin,
Deutschland
3University Cancer Centre, University Hospital Carl Gustav Carus, Dresden,
Deutschland
4Department of Internal Medicine, Johanniter Hospital, Bonn, Deutschland
5Department of Integrated Oncology, University Hospital, Bonn, Deutschland
Purpose: In oncology, adverse events (AE) are mainly documented
using the Common Terminology Criteria for Adverse Events (CTCAE)
(1). is physicians’ assessment can be supported by patient-reported
outcomes (PRO) (2). For this reason, the NCI has developed a PRO
version of the CTCAE criteria, consisting of a pool of 78 symptoms
and 124 items (3). A core item set containing 31 items for patients with
chemotherapy has already been validated in German (4). e aim of this
study was to develop tumor disease-specic PRO-CTCAE item sets for
dierent tumor entities with high content validity.
Methods: Patients treated at three outpatient centres were asked to assess
the occurrence and relevance of the 78 PRO-CTCAE symptoms using
a questionnaire. In order to select PRO-CTCAE items for each tumor
entity, individual symptoms were ranked on the basis of occurrence and
relevance.
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Results: In the nal evaluation 101 patients with breast cancer with and
without metastases (BC) and 107 patients with multiple myeloma (MM)
were analysed. e BC item set contains 39 items representing 21 symp-
toms, the MM item set 39 items for 19 symptoms. 32 items for 16 symp-
toms are included in both item sets. Four out of the ve main symptoms
with the highest raking in both item sets were fatigue, numbness and tin-
gling, sleep disorders and nausea. e symptom with the highest ranking
included only in one item set was blurred vision in the BC item set and
anxiety in the MM item set. 24 items of the core item set were included in
the MM item set, 17 items in the BC item set.
Conclusions: Based on patient-reported dierences in symptom pattern,
specic PRO-CTCAE item sets with high content validity were developed
for breast cancer and multiple myeloma. eir psychometric criteria will
be analysed in a validation study.
References:
1. NCI. CTCAE Version 5.0. 2017
2. Basch E. N Engl J Med 2010; 362: 865-869
3. Basch E et al. J Natl Cancer Inst 2014; 106: 1-11
4. Hagelstein V et al. Ann Oncol 2016; 27: 2294-2299
Disclosure Statement: e authors do not have to disclose any conicts of interest.
570
Late Toxicities and Long-Term Health-Related Quality of Life
Among Head and Neck Cancer Survivors
Katherine Taylor 1; Cecilie Delphin Amdal 2; Guro Lindviksmoen Astrup 3;
Kristin Bjordal 4; Andreas Böhm 5; Bente Brokstad Herlofson 6, 7;
Ayman Bushnak 8; Joaquim Castro Silva 9; Alexander Fabian 10;
Johanna Inhestern 11; Ulrike Mölle 5; Michaela Plath 12; Susanne Singer 13
1Institute for Medical Biostatistics, Epidemiology and Informatics, Mainz,
Deutschland
2Oslo University Hospital, Oncology Department, Oslo, Norwegen
3Oslo University Hospital, Department of Oncology / Research Support Service,
Oslo, Norwegen
4Oslo University Hospital, Institute for Clinical Medicine, Oslo, Norwegen
5St. Georg Hospital, Department of Otolaryngology, Head and Neck Surgery,
Leipzig, Deutschland
6Oslo University Hospital, Unit of Oral and Maxillofacial Surgery, Department
of Otorhinolaryngology - Head and Neck Surgery Division of Head, Neck and
Reconstructive Surgery, Oslo, Norwegen
7Oslo University, Faculty of Dentistry, Oslo, Norwegen
8University Hospital Giessen, Department of Otolaryngology, Head and Neck
Surgery, Giessen, Deutschland
9Instituto Português de Oncologia Francisco Gentil do Porto, Department of
Otolaryngology, Head and Neck Surgery, Porto, Portugal
10University Hospital Schleswig-Holstein, Radiation Therapy Department, Kiel,
Deutschland
11Oberhavel Hospital, Department of Otolaryngology, Head and Neck Surgery,
Henningsdorf, Deutschland
12University Hospital Heidelberg, Department of Otolaryngology, Head and
Neck Surgery, Heidelberg, Deutschland
13University Hospital Mainz, Institute for Medical Biostatistics, Epidemiology and
Informatics, Mainz, Deutschland
Purpose: To measure the health-related quality of life (HRQoL) and ex-
tent of treatment- and disease-related toxicities in head & neck cancer
(HNC)survivors more than 5 years’ post-treatment. e main research
questions aim to examine HRQoL dierences between the survivors and
reference HNC patient data from before treatment and 1 year post-treat-
ment and to observe the frequency of toxicities among the survivors.
Methods: In this on-going, cross-sectional study coordinated by the
University Hospital in Mainz, Germany, collaborators from 16 countries
invite eligible survivors to their clinic, where they undergo a clinical ex-
amination for toxicities (measured with the CTCAE) and ll out ques-
tionnaires on HRQoL, productivity losses, use of medical services, and
supportive care needs. is project began in September 2017 and will run
until October 2021.
Results: To date, questionnaires have been robustly translated into 11 lan-
guages and ethical approval obtained at more than 10 sites. 214 survivors
have been enrolled by 8 sites in 4 countries, with 5 more countries (7 new
sites) expected to begin enrolment during fall 2019. Project meetings have
taken place 4 times a year since the fall of 2017.
Conclusions: is project is progressing well and will provide compre-
hensive information on the long-term problems survivors deal with and
which HRQoL issues appear to improve or worsen. Examples of frequent
problems among long-term survivors include dry mouth, dysphagia, so
tissue brosis, and peripheral sensory neuropathy. An international ef-
fort provides an opportunity to enroll a large cohort of long-term HNC
survivors using standardized instruments. To date, studies on long-term
eects have oen included relatively few survivors, largely limited to sin-
gle countries.
Disclosure Statement: Nothing to disclose.
680
Impact of Oncological Therapy and Viscum Album
L. Treatment on Health Related Quality of Life in Breast
Cancer Patients
Shiao Li Oei 1; Anja Thronicke 1; Matthias Kröz 1, 2, 3; Philipp von Trott 4;
Harald Matthes 1, 4, 5; Friedemann Schad 1, 4
1Research Institute Havelhöhe, Berlin, Deutschland
2Institute of Social Medicine, Charité Universitätsmedizin Berlin, corporate
member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin
Institute of Health, Berlin, Deutschland
3Institute for Integrative Medicine, Universität Witten/ Herdecke, Witten,
Deutschland
4Interdisciplinary Oncology and Palliative Care, Hospital
Gemeinschaftskrankenhaus Havelhöhe, Berlin, Deutschland
5Institute of Social Medicine, Epidemiology and Health Economics and
Medical Department of Gastroenterology, Infectiology and Rheumatology,
Charité Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin,
Deutschland
Purpose: Viscum album L. extracts (VA) are frequently used in integrative
oncology to enhance health-related quality of life (HRQL). e key im-
plication of this study was to evaluate the impact of oncological therapies
and add-on VA applications on HRQL in breast cancer patients.
Methods: Clinical and demographic data were retrieved from the Net-
work Oncology cancer registry. Primary non-metastasized breast cancer
patients treated with oncological standard therapy alone or in combina-
tion with VA-applications were included. At rst diagnosis and 24 months
later the European Organization of Research and Treatment Health-Relat-
ed Quality of Life Core Questionnaire (EORTC-QLQ-C30) were admin-
istered and evaluated.
Results: A total of 118 patients (median age 60 years) received standard
oncological therapy, 85 patients of them (72%) endocrine therapy, 34
(29%) chemotherapy (Ctx), and 12 (10%) immunotherapy. 49 patients
(42%) received additionally VA applications. Adjusted multivariable lin-
ear regression analyses revealed for the study cohort that Ctx, immuno-,
and endocrine therapies had a worsening of 17, 17, and 6 point changes
respectively for fatigue, while VA applications showed an improvement
of 12 point change (p = 0.0004). A similar impact of worsening (standard
oncological treatment regimens) and improvement (add-on VA) on in-
somnia (p = 0.009) and physical functioning (p = 0.005) were observed.
Conclusions: In the present longitudinal real-world observational anal-
ysis Ctx, immuno-, and endocrine therapies showed a negative impact
while add-on VA applications in addition to standard therapy had a sup-
portive eect on HRQL. us, add-on VA applications might be suited
to partially alleviate discomfort symptoms during anticancer strategies in
breast cancer patients.
Disclosure Statement: Grants from Helixor Heilmittel GmbH, Iscador AG and
ABNOBA GmbH (FS). Lecturer Honorarium from Helixor Heilmittel GmbH
(MK). No competing interests (SLO, AT, PT, HM).
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The Electronic Assessment of Patient-Reported Outcomes and
Quality of Life in Radiooncology – Pilot Implementation and
Process Evaluation
Thomas Nordhausen 1; Dirk Vordermark 2; Bernhard Holzner 3, 4;
Haifa Kathrin Al-Ali 5, 6; Gabriele Meyer 1; Heike Schmidt 2, 7
1Institute of Health and Nursing Science, Martin Luther University Halle-
Wittenberg, Deutschland
2Department of Radiation Oncology, University Hospital Halle (Saale),
Deutschland
3Department of Psychiatry, Psychotherapy and Psychosomatic Medicine,
University Hospital Innsbruck, Österreich
4Evaluation Software Development, Österreich
5Department of Internal Medicine IV, University Hospital Halle (Saale),
Deutschland
6Krukenberg Cancer Center, University Hospital Halle (Saale), Deutschland
7Institute of Health and Nursing Science, Martin Luther University Halle-
Wittenberg, Halle (Saale), Deutschland
Purpose: Numerous studies have shown the benet of Patient-Reported
Outcome measurements (PROM) including Health Related Quality of
Life (HRQOL) in clinical practice. However, standardized assessments are
still not part of clinical routine. A successful implementation in clinical
practice needs a structured approach including participation of all stake-
holders/parties involved as well as understanding of clinical practice, re-
quired changes, process evaluation and training.
Methods: 1. Analysis of current practice, assessment of facilitators and
barriers of implementation; 2. Interprofessional focus groups to decide on
PROMs, assessment times and clinical pathways; 3. Development of face
to face training and e-learning for clinical sta; 4. Stepwise implementa-
tion for in-patients and out-patients; 5. Process evaluation and optimiza-
tion; 6. Evaluation of impact.
Results: e still ongoing project is currently in phase 4. Sta decided on
initial assessment of HRQOL (EORTC QLQ C30) followed by daily mon-
itoring of a core set of eleven symptoms combined with few site specic
questions based on EORTC single items and a nal assessment of HRQOL
at the end of the treatment. Developed guidelines how to react to symp-
toms are accessible for clinicians to ensure quality of care and to facili-
tate communication with patients. e electronic questionnaires are well
accepted by patients and facilitate documentation and allocation of sup-
portive measures. Process evaluation shows, that time, interprofessional
communication and continuous support is needed to achieve changes of
clinical routine. Support by clinic IT is crucial to guarantee success.
Conclusions: e integration of the electronic assessment of HRQOL
into clinical practice is facing some challenges due to the complexity of
the implementation process. A manual based on the results of the process
evaluation, consisting of the many aspects that have to be considered, can
support further implementations in other oncological settings.
Disclosure Statement: Bernhard Holzner holds IPRs on the PROM soware
CHES.
792
Health-Related Quality of Life and Psychosocial Well-Being in
Cancer Survivors >10 Years Past Diagnosis
Daniela Doege 1; Melissa Thong 1; Linda Weißer 2; Lena Koch-Gallenkamp 2;
Lina Jansen 2; Heike Bertram 3; Andrea Eberle 4; Bernd Holleczek 5;
Ron Pritzkuleit 6; Annika Waldmann 7; Sylke Zeißig 8; Hermann Brenner 2, 9, 10;
Volker Arndt 1
1German Cancer Research Center (DKFZ), Unit of Cancer Survivorship, Division
of Clinical Epidemiology and Aging Research, Heidelberg, Deutschland
2German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and
Aging Research, Heidelberg, Deutschland
3Cancer Registry of North Rhine-Westphalia, Bochum, Deutschland
4Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen
Cancer Registry, Bremen, Deutschland
5Saarland Cancer Registry, Saarbrücken, Deutschland
6Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland
7Ministry of Health and Consumer Protection, Hamburg Cancer Registry,
Hamburg, Deutschland
8Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland
9German Cancer Research Center (DKFZ), Division of Preventive Oncology,
Heidelberg, Deutschland
10German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK),
Heidelberg, Deutschland
Purpose: Little is known about health-related quality of life (HRQoL) in
very long-term cancer survivors >10years past diagnosis. It is of great
interest, whether these survivors’ HRQoL diers from that of the gener-
al population and to which extent cancer still plays a role in their lives.
Study objectives were (1) to compare cancer survivors’ HRQoL to that
of non-cancer controls, and (2) to assess the prevalence of (a) fear of re-
currence (FoR), (b) cancer burden, and (c) the self-identity of still being
a cancer patient.
Methods: e samples of 2713 breast, colorectal and prostate cancer sur-
vivors (13–23years post-diagnosis) and 1765 controls were recruited in
German multi-regional population-based studies. HRQoL was assessed
by the European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Dierences
in HRQoL were assessed with multiple regression, controlling for age and
education. FoR was assessed with PAF-KF (Progredienzangst-Fragebogen
Kurzform). Patient identity and cancer burden were assessed by single
item questions.
Results: Cancer survivors overall QoL/ global health status was slightly
higher than that of same-age general population and they reported less
pain. However, they perceived a slightly lower social function, and more
dyspnea, constipation, and diarrhea. 12% of cancer survivors reported
high FoR (moderate fear: 19%). Although 75% reported that their treat-
ment had ended, 17% of those still felt as a cancer patient. A low, moderate
or high burden of the cancer on their current lives was reported by 46%
of all survivors.
Conclusions: Most functioning aspects of very long-term cancer sur-
vivors were comparable to same-age population controls. A majority of
cancer survivors reported a low FoR and a small symptom burden. How-
ever, even many years aer end of treatment, cancer-related symptoms
and fears still play a role in survivors’ lives. e need of continuous care
aer the end of regular treatment, including psychosocial aspects, seems
to be warranted.
Disclosure Statement: No conict of interest.
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803
Health-Related Quality of Life in Long-Term Survivors of
Metastatic Cancer
Volker Arndt 1; Lena Koch-Gallenkamp 2; Daniela Doege 1; Melissa Thong 1;
Heike Bertram 3; Andrea Eberle 4; Bernd Holleczek 5; Ron Pritzkuleit 6;
Annika Waldmann 7, 8; Sylke Zeißig 9; Lina Jansen 2; Hermann Brenner 2, 10, 11
1Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging
Research, German Cancer Research Center (DKFZ), Heidelberg, Deutschland
2Division of Clinical Epidemiology and Aging Research, German Cancer
Research Center (DKFZ), Heidelberg, Deutschland
3Cancer Registry of North Rhine-Westphalia, Bochum, Deutschland
4Bremen Cancer Registry, Leibniz Institute for Prevention Research and
Epidemiology - BIPS, Bremen, Deutschland
5Saarland Cancer Registry, Saarbrücken, Deutschland
6Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland
7Hamburg Cancer Registry, Ministry of Health and Consumer Protection,
Hamburg, Deutschland
8Institute of Social Medicine and Epidemiology, University Lübeck, Lübeck,
Deutschland
9Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland
10Division of Preventive Oncology, German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
11German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
Purpose: e challenges of cancer survivors have gained increasing at-
tention in recent years. However, most pertinent publications focused on
survivors with cancer in remission. In contrast, long-term survivors with
metastatic cancer have not been well studied. In this study, we describe
health related quality of life (HRQoL) in long-term survivors aer diag-
nosis of metastatic cancer in comparison to non-metastatic survivors and
population controls.
Methods: 6952 long-term cancer survivors (5-16 years past diagnosis
of breast [n=3045], colorectal [n=1504], or prostate cancer [n=2403]),
recruited in the population-based CAESAR + study, were compared ac-
cording to tumor stage with 1878 cancer free controls from the German
general population. Stage at diagnosis could be classied into localized
[n=3984], regional [n=1821], and localized disease [n=129] in 5934 cancer
survivors. HRQoL was assessed by the EORTC QLQ-C30. e association
between tumor stage and HRQoL was analyzed using multiple regression
while controlling for age, gender, and education. Supplemental analyses
were employed to assess the impact of disease recurrence on HRQoL.
Results: Long-term survivors with distant disease reported signicantly
poorer global health and quality of life across multiple dimensions includ-
ing physical, role, and social functioning and more nancial diculties
and symptoms such as fatigue, insomnia, and dyspnea than survivors with
regional metastases or localized disease as well as population controls (all
p< 0.01). Recurrence of disease occurred more oen among survivors
with distant cancer (36%) than among survivors with regional (17%) or
localized disease (11%) and was strongly associated with poorer HRQOL.
However, recurrence of disease did not fully explain the detriments in
HRQOL in survivors with distant cancer.
Conclusions: Cancer survivors with either metastatic disease or disease
recurrence suer in particular from long-lasting detriments in HRQoL.
e experience of these survivors should not be neglected in cancer sur-
vivorship research.
813
Adolescents and Young Adults are at Risk for Psychosocial
Sequelae after Cancer Treatment
Andreas Wittwer 1; Peter Kropp 2; Kristin Pulewka 3; Andreas Hochhaus 1;
Inken Hilgendorf 1
1Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische
Onkologie, Universitätsklinikum Jena, Jena, Deutschland
2Institut für Medizinische Psychologie und Medizinische Soziologie,
Universitätsmedizin Rostock, Rostock, Deutschland
3Institut für Psychosoziale Medizin und Psychotherapie, Universitätsklinikum
Jena, Jena, Deutschland
Purpose: Adolescents and young adults (AYA) who survive cancer are at
high risk for psychological and social sequelae. Aiming to explore unmet
needs and psychosocial distress, we performed a survey among all AYA
treated for a haematological malignancy at our center since January 2010.
Methods: 85 AYA-survivors were invited to join the survey; at median
of 36 (2-86) months aer completion of therapy. A set of standardized
screening instruments for psychosocial stressors (PhQ-S), symptoms of
depression (PHQ-9), generalized anxiety (GAD7), fear of progression
(PAF-KF), quality of life (EORTC QLQ-C30) and a self-designed ques-
tionnaire were sent to the patients.
Results: Data from a total of 47 (20 male) patients were available. Median
age was 35 years. e mean on all QLQ-C30 function scales was less than
published for a control group [1]. In addition, 51% of the participants re-
ported on psychosocial stressors (PHQ-S), 45% had depression symptoms
(PHQ-9) and 36% suered from anxiety symptoms (GAD-7). Unemploy-
ment correlated with PHQ-S (p = 0.029), PHQ-9 (p=0,025) and GAD-7
(p = 0.006). In contrast, employment was a strong predictor for higher
quality of life (p < 0.001). A high fear of disease progression (PAF12, cut-
o 34) was reported by 36% of survivors. e fear of disease progression
correlated with a lower level of education (p = 0.026) and with having
children (p = 0.027). Strain was also caused by psychosocial issues emerge
from daily life topics, e.g. the majority of patients (72%) reported on di-
culties on resumption to work and 62% had problems with sexuality.
Conclusions: Our results clearly indicate that AYA feature a high bur-
den for psychosocial distress aer cancer treatment. In order to improve
quality of life, resumption of work is of utmost importance. erefore,
psycho-oncological and social support needs to become an inherent part
in the aercare of AYA patients.
Reference:
1. Geue et al. Qual Life Res (2014) 23:1377–1386
Disclosure Statement: IH is member of the board of trustees of the German
Foundation for Young Adults with Cancer.
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2018
Radiation
Vorträge
614
Balloon Catheters to extend the Distance between Tumor and
Adjacent Organs at Risk in Interstitial HDR-Brachytherapy of
Liver Malignomas
Peter Hass 1; I.G. Steen 2; Maciej Janusz Powerski 3; Konrad Mohnike 4;
Max Seidensticker 5; Frank Meyer 6; C. Willich 7; Mathias Walke 1;
E. Karagiannis 1; Günther Gademann 1; Thomas Brunner 1; Jens Ricke 5
1Department of Radiation Oncology, University Hospital at Magdeburg,
Magdeburg, Deutschland
2Department of Nuclear Medicine, University Medical Center Charité at Berlin,
Berlin, Deutschland
3Department of Radiology and Nuclear Medicine, University Hospital at
Magdeburg, Magdeburg, Deutschland
4International School of Image-Guided Interventions, Magdeburg, Deutschland
5Department of Clinical Radiology, Ludwig-Maximilian University (LMU) at
Munich, Munich, Deutschland
6Dept. of General, Abdominal, Vascular and Transplant Surgery, University
Hospital at Magdeburg, Magdeburg, Deutschland
7Department of Radiation Therapy and Radiooncology, University Hospital at
Jena, Jena, Deutschland
Purpose: Organs at risk (OAR), which are very close to a clinical target
volume (CTV) can prevent an eective irradiation of the tumor without
a signicant risk of serious side eects. e present study investigated the
extent of the dosimetric eect of distancing CTV from adjacent OARs by
means of interventionally applied balloon catheters.
Methods: Consecutive patients with peripheral, predominantly le lobu-
lar hepatic malignancies, which revealed the critical proximity of an OAR
to the CTV in the assessment by gadoxetic acid-enhanced MRI-scans and
the preplanning process, underwent also placement of an interventional
balloon catheter during CT-guided application of interstitial brachythera-
py catheters inserted into the tissue between hepatic capsule and adjacent
OAR. e virtual position of the OAR without balloon catheter was an-
ticipated and contoured in addition to contouring of CTV (which is equal
to Planning Target Volume [PTV] in brachytherapy), liver and further
relevant OAR. e calculated dose values for CTV as well as 1 mL of the
relevant OAR (D1cc) with and without balloon were recorded. e D1cc
of the realized irradiation plan was compared to the D1cc of the virtually
contoured OAR and statistically evaluated.
Results: In 31 cases, one balloon catheter (in 6 cases two) was adminis-
tered without any acute complications. e total duration of the applica-
tion time was increased by 5 min per balloon catheter. Serious late side
eects occurred in one (3%) case only. e median D1cc in the group with
balloon (13.5 Gy) was signicantly lower compared to the virtual OAR
group without a balloon (15.5 Gy) with a corresponding median relative
dierence of -16.3%.
Conclusions: e achievable, signicantly lower dose exposition of the
adjacent OAR reduces the risk of side eects. is may be particularly
important in case of oligo-metastasis since a more ecient irradiation of
the CTV becomes possible consecutively.
Disclosure Statement: Nothing to be disclosed.
Poster
37
Intensity Modulated Radiotherapy (IMRT) with Carbon
Ion Boost in the Multimodal Treatment of Salivary Duct
Carcinoma
Sebastian Adeberg 1; Paul Windisch 2; Felix Ehret 1; Melissa Baur 1;
Sati Akbaba 1; Thomas Held 1; Denise Bernhardt 1; Matthias Haefner 1;
Jürgen Krauss 3; Steen Kargus 4; Christian Freudlsperger 4; Peter Plinkert 5;
Christa Flechtenmacher 6; Klaus Herfarth 1; Jürgen Peter Debus 1;
Stefan Rieken 1
1Radioonkologie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
2Radioonkologie, Zürich, Schweiz
3Medizinische Onkologie, Universitätsklinikum Heidelberg, Heidelberg,
Deutschland
4MKG, Universitätsklinikum Heidelberg
5HNO, Universitätsklinikum Heidelberg, Deutschland
6Pathologisches Institut, Universitätsklinikum Heidelberg
Purpose: To assess outcomes and treatment related toxicity following in-
tensity-modulated radiotherapy (IMRT) and a Carbon Ion Radiotherapy
(CIRT) boost for salivary duct carcinoma (SDC).
Methods: Twenty-eight consecutive patients with SDC who underwent a
postoperative (82%) or denitive (18%) radiation therapy between 2010
and 2017 were assessed in this retrospective single-center analysis. CIRT
boost was delivered with median 18 Gy(RBE) in 6 daily fractions, followed
by an Tomoerapy®-based IMRT (median 54 Gy in 27 daily fractions).
Treatment-related acute toxicity was assessed according to CTCAE Ver-
sion 4.
Results: Tumors were most commonly located in the major salivary
glands (n=25; 89%); 23 patients (82%) received previous surgery (R0:
30%; R1: 57%; R2: 4%; RX: 19%). Median follow-up was 30 months. Four
patients (14%) patients experienced a local relapse and 3 (11%) developed
locoregional recurrence. e two-year local control (LC) and locoregional
control (LRC) was 96% and 93%, respectively. Median disease-free surviv-
al (DFS) was 27 months, metastasis-free survival (MFS) was 69 months,
and overall survival (OS) was 93 months. Acute grade 3 toxicity occurred
in 11 patients (mucositis, dermatitis, xerostomia; n=2 each (7%) were the
most common) and 2 osteonecrosis of the mandibular (grade 3) occurred.
No patients experienced grade ≥4 toxicities.
Conclusions: Multimodal therapy approaches with surgery followed by
IMRT and CIRT boost for SDC leads to good local and locoregional dis-
ease control. However, the frequent occurrence of distant metastases lim-
its the prognosis and requires optimization of adjuvant systemic therapies.
Disclosure Statement: Nothing to declare.
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2018
170
Teaching Radiation Oncology to Medical Students in Germany
Where do we Stand?
Michael Oertel 1; Matthias Mäurer 2; Daniel Fleischmann 3;
Christian Dietzel 4; David Krug 5
1Universitätsklinikum Münster, Klinik für Strahlentherapie - Radioonkologie,
Münster, Deutschland
2Universitätsklinikum Jena, Klinik für Strahlentherapie und Radioonkologie,
Jena, Deutschland
3Klinikum der LMU München, Klinik und Poliklinik für Strahlentherapie und
Radioonkologie, München, Deutschland
4Universitätsklinikum Halle(Saale), Klinik und Poliklinik für Strahlentherapie,
Halle (Saale), Deutschland
5Universitätsklinikum Schleswig-Holstein – Campus Kiel , Klinik für
Strahlentherapie, Kiel, Deutschland
Purpose: To measure and analyse the teaching situation for radiation on-
cology (RO) in Germany.
Methods: A detailed questionnaire containing multiple-choice and free
text questions covering extent and topics of RO was sent to RO depart-
ments at all university hospitals in Germany and answered by the head of
departments/main lecturers.
Results: 24/35 (68.6%) of RO departments returned completed forms.
Overall, RO plays a role in the curriculum from the 2nd semester onward
with the majority of teaching from the 5th to 10th semester. Most faculties
employ lectures (91.7%), seminars (87.5%) and practical/bedside train-
ing (75.0%), whereas training in radiation biology and medical physics
are less common (25% and 33.3%, respectively). Main topics covered are
general RO (100%), radiation biology (91.7%) and side eects (87.5%).
Concerning dierent organ systems gynaecological (87.5%), urological
(79.2%) and gastroenterological tumors (75%) ranked highest and were
also the predominant subjects for interdisciplinary concepts. Regarding
RO techniques, image-guided and intensity-modulated radiotherapy has
taken centre stage being taught at all faculties, followed by palliative RO
and stereotactic techniques (87.5% each). Notably, all departments oered
a partial rotation (“Wahltertial”) in RO in conjunction with Radiology
and/or Nuclear Medicine departments in the last year of medical school,
while only 70.8% oered a complete rotation in RO. In addition, 57.1%
have taken measures concerning the coming National Competence-based
Learning Objectives Catalogue for medical education.
Conclusions: RO has an integral role in the (clinical) medical education
in Germany, but faces new challenges regarding the development of a
practical, competence-based education, which may require both innova-
tive and interdisciplinary concepts [1,2].
References:
1. Jünger J 2018 Feb;61(2):171–7.
2. Oertel M et al. Strahlenther Onkol. 2019 Jul DOI: 10.1007/s00066-019-01492-z
Disclosures: MO and MM are members of the working group “Medizinstudium
of the DEGRO.
187
Analyzing Oral Sequelae of Chemo-Radio-Therapy in the
Head-Neck-Region
Benedikt Luka 1; Hatice Bunea 2; Andreas Thomsen 2;
Elsa Beatriz Monroy Ordonez 2; Sibylle Rau 1; Alice Eickenscheidt 3;
Michael Henke 2; Nadine Schlüter 1
1Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-
Universität Freiburg, Deutschland, Department f. Zahn-, Mund- u.
Kieferheilkunde, Klinik für Zahnerhaltungskunde und Parodontologie,
Stiftungsprofessur für Kariesforschung, Freiburg im Breisgau, Deutschland
2Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-
Universität Freiburg, Deutschland, Department für Radiologische Diagnostik
und Therapie, Klinik für Strahlenheilkunde, Freiburg im Breisgau, Deutschland
3Institut für Mikrosystemtechnik – IMTEK, Albert-Ludwigs-Universität, Freiburg
Centre for Interactive Materials and Bioinspired Technologies (FIT) and
Department of Microsystems Engineering, Polymer Synthesis and Surface
Engineering Group, Freiburg im Breisgau, Deutschland
Purpose: Side-eects of chemo-radio-therapy (CRT) of the head-neck-
region can severely impair patients. ere is limited knowledge on
interdependencies of side-eects. A better understanding of underlying
mechanisms, however, may help improving supportive care of these
patients. We intend to study interactions of mucosal, salivary, dental and
cellular parameters of patients with head-neck-cancer during and aer
CRT in an interdisciplinary setting. e study protocol and rst results of
the pilot stage will be presented.
Methods: Patients (n=50) undergoing curative CRT in the head-neck-
region (cisplatinum 2x100mg/m2; 60-70 Gy; 5x2 Gy/week) are examined
one week before, during, at the end, and 8 and 20 weeks aer CRT. A pre-
treatment oral mucosa biopsy is taken for cellular radiosensitivity testing.
On exam1-5 (Ex1-Ex5) mucositis is scored (severity 0-5), saliva collected
(stimulated/unstimulated; ow rate, pH, buering capacity, microbiome,
proteome), dental status assessed (plaque index, pocket depth, bleeding
on probing, caries status (ICDAS)) and quality of life surveyed (xerosto-
mia inventory, quality of life (OHIP-14), food intake frequency, oral hy-
giene). Age/gender matched healthy controls are also included (n=25, no
CRT).
Results: First results (n=11) showed increasing mucositis during CRT
(Ex3: +2.2 points) that almost completely recovered aer CRT. Both, stim-
ulated and unstimulated saliva ow rates were reduced during (Ex3: -71%
and -42%) and stayed constantly low aer CRT (Ex5: -75% and 50%).
Caries-Scores increased constantly during and aer CRT (Ex3: +9.1, Ex5:
+36.9).
Conclusions: CRT impacted most investigated parameters. Our rst re-
sults warrant further evaluations of these factors and their interactions to
ultimately develop strategies aimed to attenuate the grievous side-eects
of CRT in patients with head-neck-cancer.
Disclosure Statement: Funding: University of Freiburg. Previous presentation in
parts: 96th/97th General Session of the IADR 2018/2019, 4. DGZ Tag der Wissen-
scha/Universitäten 2018.
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2018
261
Evaluation of High-Risk Imaging Features for Detection of
Local Progression after Stereotactic Body Radiotherapy
(SBRT) of Malignant Pulmonary Lesions in the Prospective
Stripe -Trial
Sonja Adebahr 1, 2, 3; Katharina Wagner 1; Thomas Brunner 4; Eleni Gkika 1;
Hans-Christian Rischke 1; Juri Ruf 5; Anca-Ligia Grosu 1, 2, 3; Werner Vach 6;
Ursula Nestle 1, 7
1Department of Radiation Oncology, Medical Center, Faculty of Medicine,
University of Freiburg, Freiburg, Germany
2German Cancer Consortium (DKTK) Partner Site Freiburg, Germany
3German Cancer Research Center (DKFZ), Heidelberg, Germany
4Department of Radiotherapy, University of Magdeburg, Magdeburg, Germany
5Department of Nuclear Medicine, Freiburg University Medical Center, Freiburg,
Germany
6Department of Orthopaedics and Traumatology, University Hospital Basel,
Basel, Switzerland
7Department of Radiation Oncology, Kliniken Maria Hilf GmbH
Mönchengladbach, Möchengladbach, Germany
Purpose: Detection of local progression (LP) aer stereotactic body
radiotherapy (SBRT) for lung lesions can be dicult because of radia-
tion-induced lung changes in CT scans. High–risk CT-features (HRF-CT)
for prediction of LP have been proposed, the role of 18F-FDG-PET re-
mains unclear. Here previously dened HRF-CT and 18F-FDG-PET-im-
aging features were evaluated in a prospective SBRT-trial cohort (STRIPE)
under “real-life conditions.
Methods: Four independent and blinded observers scored follow-up
(FU)-CT and 18F-FDG-PET/CT images of 65 pulmonary lesions aer
SBRT with a structured questionnaire assessing RECIST and HRF-CT
((sequential) enlarging opacity, bulging margin, linear margin disap-
pearance, loss of air bronchogram, craniocaudal growth). If LP was sus-
pected, the respective18F-FDG-PET images were analyzed qualitatively,
then quantitatively. Sensitivity and specicity of HRFs for detecting LP
were calculated using the reference standard dened by clinical long term
courses, including information on imaging and biopsy. Inter-observer
Agreement (IOA) was determined using Cohens kappa.
Results: IOA for presence of individual HRF-CT were “slight” (k=0.119
to k=0.288), for overall suspicion on LP aer CT assessment k= 0.308 for
HRF-CT, k= 0.289 for RECIST and k= 0.604 aer qualitative additional
PET assessment. Sensitivity and specicity were 0.22-0.46 and 0.73-0.92
for HRF-CT, 0.30 and 0.94 for RECIST. Additional qualitative 18F-FDG-
PET/CT analysis was highly sensitive (1.0; specicity 0.79), semi-quan-
titative evaluation using SUVmax revealed no further diagnostic benet
(sensitivity 1.0; specicity 0.67). Sensitivity / specicity of CT-assessment
versus qualitative PET-assessment were 0.43 / 0,86 and 1,0 / 0,85, respec-
tively.
Conclusions: While we could neither conrm RECIST nor dened HRF-
CT as reliable predictors of LP, qualitative 18F-FDG-PET/CT assessment
seems to oer more diagnostically accurate information about LP aer
SBRT, not being improved by quantitative 18F-FDG uptake analysis.
263
Immunomodulatory Eects of Photon and Carbon Ion
Irradiation – A Dierentialin Vitro Analysis
Philipp Schröter 1, 2, 3, 4; Laura Hartmann 2; Wolfram Osen 2;
Daniel Baumann 5, 6; Rienk Oringa 5, 6; Stephan Brons 3, 4; Jürgen Debus 1, 3, 4;
Stefan B. Eichmüller 2; Stefan Rieken 1, 3, 4
1Heidelberg University Hospital (UKHD), Department of Radiation Oncology,
Heidelberg, Deutschland
2German Cancer Research Center (DKFZ), Research Group GMP & T Cell Therapy,
Heidelberg, Deutschland
3Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Deutschland
4Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Deutschland
5German Cancer Research Center (DKFZ), Molecular Oncology of
Gastrointestinal Tumors, Heidelberg, Deutschland
6Heidelberg University Hospital (UKHD), Department of Surgery, Heidelberg,
Deutschland
Purpose: We compared the immunomodulatory eects of single photon
doses on the murine pancreatic ductal adenocarcinoma (PDA) cell line
PDA30364/OVA to high-LET radiation with carbon (12C) ions in vitro.
Methods: Cells were irradiated by a Gammacell 40 Exactor device (pho-
tons) or through the experimental beam line of the HIT (12C ions). Bio-
logically eective doses (BED) were established through dose dependent
relative biological eectiveness (RBE), determined by clonogenic survival
assay. Cell surface expression of immunomodulatory molecules as well as
cell cycle analyses on PI stained cells were performed by ow cytometry.
Sensitization of target cells for cytotoxic T cell (CTL) mediated lyses was
analyzed via impedance-based cytotoxicity assay.
Results: Dose dependent RBE for 1, 3, 5 and 10 Gy photons were dened
as 10, 7.5, 5 and 3.23, respectively, resulting in equivalent physical doses
of 0.1, 0.4, 1.0 and 3.1 Gy 12C ions. Irradiation induced a dose dependent
G2/M cell cycle arrest and a moderate increase in cell surface expres-
sion of PD-L1, CD73 and MHC class I molecules. CTL mediated lysis of
PDA30364/OVA cells was signicantly increased at higher doses, however
additional checkpoint blockade of PD-L1 did not further enhance target
cell killing signicantly. Eects of 12C ions were generally milder at doses
≤ 5 Gy (BED) reaching an equivalent magnitude at 10 Gy (BED).
Conclusions: Raising single photon doses ≥ 5 Gy, PDA cells were respon-
sive to irradiation with respect to classical radiobiology endpoints and,
moreover, to enhanced CTL mediated target cell killing, thus suggesting
a superiority of hypofractionation over normofractionated regimens. Ir-
radiation with high-LET carbon ions yielded comparable results, however
only at enhanced doses of 10 Gy (BED) with RBE = 3.23. Our data suggest
that the discrepancies among the irradiation eects observed are most
likely caused by the equivalent dose denition via clonogenic survival,
strictly applying a dose dependent RBE.
Disclosure Statement: nothing to disclose.
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2018
672
Carbon-Ion Beam Radiotherapy (C12 RT) as Part of a Trimodal
Therapy for Non-Small Cell Pancoast Tumors: The INKA-Study
Lukas Schaub 1, 2; Henrik Hauswald 1, 2; Hauke Winter 3; Peter Schirmacher 4;
Michael Thomas 5; Uwe Haberkorn 6; Ellerbrock Malte 2; Jürgen Debus 1, 2;
Klaus Herfarth 1, 2
1Department of Radiation Oncology, University Hospital Heidelberg,
Deutschland
2Heidelberg Ion-Beam Therapy Center (HIT), University Hospital Heidelberg
3Department of Surgery, Thoraxklinik, University Hospital Heidelberg,
Deutschland
4Institute of Pathology, University Hospital Heidelberg, Deutschland
5Translational Lung Research Center Heidelberg (TLRC-H), Member of the
German Center for Lung Research (DZL), Thoraxklinik im Universitätsklinikum
Heidelberg
6Department of Nuclear Medicine, University Hospital Heidelberg, Deutschland
Purpose: Pancoast-tumors are rare bronchogenic tumors arising from the
lung apices and inltrating surrounding tissue. A trimodal therapy is gold
standard for locally advanced tumors. is study aims to demonstrate
safety and feasibility of hypofractionated C12 RT within the trimodal
approach.
Methods: INKA is an ongoing prospective, monocentric pilot-study at
the University of Heidelberg. Primary endpoint is safety and feasibility,
characterized by the incidence of grade 3/4 toxicities or treatment inter-
ruptions. Patients are treated with chemotherapy (CHT) according to lo-
cal standard (cisplatin/vincristine). Concomitant with the second cycle,
patients receive C12 RT to the primary tumor and PET-positive lymph
nodes. Median dose is 39 Gy (RBE) in 13 fractions. Surgery is performed
2-3 weeks aer RT. Metabolic response (PERCIST) is assessed by FDG-
PET at inclusion and before surgery. Histopathological remission is
judged according to the Junker classication.
Results: Since 2015, 11 patients were enrolled. 2 drop-outs were regis-
tered at the time of analysis; reasons were subsequent contraindication
for CHT and insucient tolerance of immobilization. None of the treated
patients showed grade ≥3 toxicities. PET-scans performed before surgery
showed partial metabolic remission, i.e. >30% decrease in SUVmax, in
6 patients (67%); 2 patients (22%) showed no change in FDG-uptake; 1
patient (11%) showed complete remission. Histopathological response
was assessed on the resected tissue and showed tumor regression of at
least Junker IIa in all patients. 5 patients (56%) were classied Junker IIb
(<10% vital tumor cells) and 2 patients (22%) showed complete regression
(Junker III).
Conclusions: First results of the ongoing INKA-trial demonstrate that
hypofractionated C12 RT as part of the trimodal therapy is well tolerated
and associated with excellent metabolic and histopathological response
shortly aer neoadjuvant therapy.
Disclosure Statement:rderung: DFG – KFO214.
686
Intracellular Brachytherapy with 32P-Doped Nanodiamonds
Helmut Bühler 1; Pascaline Nguemgo-Kouam 1;
Bettina Priesch-Grzeszkowiak 1; Anja Grillenberger 1; Mahtab Lashgari 1;
Irenäus A. Adamietz 2
1Institut f. Molekulare Onkologie und Radiobiologie, Marien Hospital, Herne,
Deutschland
2Klinik für Radiotherapie und Radio-Onkologie, Marien Hospital Herne, Herne,
Deutschland
Purpose: Nanodiamonds (NDs) are biocompatible and are therefore suit-
able as carriers for drugs such as cytostatics in cancer therapy. We have
investigated whether they are also suitable as carriers for a radionuclide
that could be used for “intracellular brachytherapy”. erefore the nano-
diamonds were doped with the strong beta-emitter 32P.
Methods: e studies were performed with cultured human breast carci-
noma and glioblastoma cells. As vitality parameters proliferation, motility
and clonogenic survival were determined. e intracellular localization
was analyzed with commercial uorescence-labelled NDs using a uores-
cence microscope.
Results: Investigations with naked NDs showed that no impairment of
the vitality parameters of the cells was observed aer endocytosis. When
32P-NDs with an activity as low as 13 Bq were taken up, proliferation and
especially clonogenic survival were severely reduced, but motility was not
impaired. e eect was signicantly more pronounced in breast cancer
cells than in glioblastoma. e observed intracellular localization of NDs,
which was predominantly perinuclear in breast cancer but more distant
cytosolic in glioblastoma, is consistent with these ndings.
Conclusions: In our model system NDs are not cytotoxic and therefore
suitable for therapy. Doped with a radionuclide, they open up a prom-
ising new option in intracellular brachytherapy. 32P seems particularly
suitable for this purpose due to the high-energy beta radiation and the
short half-life. Targeting to the malignant cells could be achieved via cou-
pled antibodies against specic surface markers of these cells, such as the
HER2 receptor in breast cancer, where a humanized therapeutic antibody
is already available.
Disclosure Statement: Nothing to declare.
697
Outcome and Toxicity after Postoperative Radiotherapy in
Patients with Squamous Cell Carcinoma of the Lip
Kristin Lang
Radioonkologie, Heidelberg, Deutschland
Purpose: Carcinomas of the lips are a relatively common malignancy of
the head and neck region, accounting for roughly one quarter of all oral
cavity cancers. Studies showed ve year survival rates between 85-95%
(1). is study summarizes our institutional experience in utilizing post-
operative RT for patients with squamous cell carcinoma (SCC) of the lips.
Methods: Between 2005 and 2018, 19 patients were postoperative treated
at the University Hospital of Heidelberg for SCC of the upper and lower
lip with a radiotherapy. Median age at diagnosis was 67years (58% male,
42% female). All patients received a median cumulative dose of 66 Gy
(range, 60-70 Gy). Median follow-up was 5.2 years.
Results: e 2-year Kaplan-Meier estimates for OS, PFS, and LDFS were
78.9%, 85.7%, and 100.0%, respectively, and 5-year OS, PFS, and LDFS
rates were 61.4%, 85.7%, and 100.0%, respectively. At the last follow-up,
13 patients (68.4%) were still alive. No patient developed locoregional
relapse; distant relapse was found in two patients (10.5%, distant lymph
nodes and skin metastasis), which occurred in a median of 15 months
aer RT. e analysis showed a signicantly better OS in patients with
higher total RT doses (>60Gy).
Conclusions: Our results demonstrate excellent local control and OS with
acceptable toxicity when utilizing adjuvant radiotherapy in patients with
SCC of the upper and lower lip, despite unfavorable characteristics (T, N,
ECE+).
Reference:
1. Lang K et al., 2018, Intensity Modulated Radiotherapy (IMRT) + Carbon Ion
Boost for Adenoid Cystic Carcinoma of the Minor Salivary Glands in the Oral
Cavity, Cancers
Disclosure Statement: e authors declare no conict of interest.
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738
The Role of Blood Biomarkers in Radiation Therapy for
Thoracic Malignancies
Eleni Gkika 1; Sonja Adebahr 1; Anton Brenner 2; Tanja Schimek-Jasch 1;
Gabriele Niedermann 1; Ursula Nestle 1, 3; Dan G. Duda 4; Anca-Ligia Grosu 1
1University Medical Center Freiburg, Department of Radiation Oncology,
Freiburg im Breisgau, Deutschland
2Ortenau Klinikum Oenburg-Gengenbach, Anästhesie, Deutschland
3Kliniken Maria Hilf GmbH, Department of Radiation Oncology,
Mönchengladbach, Deutschland
4´Massachusetts General Hospital and Harvard Medical School, E. L. Steele
Laboratories for Tumor Biology, Department of Radiation Oncology, Boston,
United States
Purpose: Radiation (RT) of malignant tumors has the potential to induce
immunomodulatory and vascular eects, which can inuence anti-tumor
immunity and normal tissue radiosensitivity. We prospectively evaluated
the role of dierent chemokines and cytokines in patients treated with
radiotherapy for dierent thoracic malignancies concerning survival (OS)
and development of RT induced lung toxicity (RILT).
Methods: Fiy-six patients with lung cancer (n=41), esophageal cancer
(n=14) or thymoma (n=1) treated either with conventionally fractionated
(n=43) or hypo-fractionated (n=13) RT were enrolled prospectively in the
study. Serum levels of IL-10, IFN-γ, IL-12p70, IL-13, IL-1β, IL-4, IL-6,
IL-8, TNF-α, bFGF, Flt-1, PlGF, VEGF, VEGF-C, VEGF-D were analyzed
by multiplex array (MesoScale Discovery) and measured in a USA CLIA-
certied core at predened time points: before, during and at the end of
RT as well as in the rst and second follow-up. Toxicities were scored
according to common toxicity criteria for adverse events.
Results: We observed upregulation of IL-10, IFN-γ, PlGF, VEGF-D and
downregulation of IL-8, TNF-α, VEGF, VEGF-C during and at the end of
RT. IL-6 was up-, Flt-1 downregulated during RT and down- respective-
ly upregulated at the end of treatment. A higher concentration of IL13,
IL-6 (both p<0.000), IL-1β (p=0.004), IL-8 (p=0.009) and bFGF (p<0.000)
during RT and of IL-6 at the rst follow up (p=0.001) correlated with OS.
Seventeen patients (30%) developed radiologic signs of RILT Grade ≥1
but only two of them (3.6%) developed clinical symptoms (Grade 2). We
could not nd any association between the dierent serial blood biomark-
ers and a higher incidence of RILT.
Conclusions: In our study early changes in blood biomarkers during RT
indicate an early immune response and might play a role in the outcome
of the treatment but don’t seem to contribute signicantly in the develop-
ment of early stage (grade 1) RILT.
739
Stereotactic Body Radiotherapy vs Transarterial
Chemoembolisation in Locally Advanced Hepatocellular
Carcinoma (Heracles: Hepatocellular Carcinoma Stereotactic
Radiotherapy Clinical Ecacy Study)
Eleni Gkika 1; Dominik Bettinger 2; Michael Schultheiss 2; Lars Maruschke 3;
Nico Bartl 1; Simon Kirste 1; Fabian Bamberg 3; Gabriele Ihorst 4;
Robert Thimme 2; Anca-Ligia Grosu 1; Thomas Brunner 1, 5
1University Medical Center Freiburg, Department of Radiation Oncology,
Freiburg im Breisgau, Deutschland
2University Medical Center Freiburg, Department of Internal Medicine, Freiburg
im Breisgau, Deutschland
3University Medical Center Freiburg, Department of Radiology, Freiburg im
Breisgau, Deutschland
4Freiburg University Hospitals, Trial Center - Biometrics, Deutschland
5University Hospitals Magdeburg, Department of Radiation Oncology,
Magdeburg, Deutschland
Purpose: Aim of this prospective trial (HERACLES Study) was to eval-
uate the role SBRT in comparison to TACE in patients with locally ad-
vanced hepatocellular carcinoma (HCC).
Methods: Patients who were discussed in a multidisciplinary tumour
board over a predened period of 12 months were included in the study.
Patients received SBRT when TACE was contraindicated, in case of
progressive disease aer TACE or when TACE was rejected by the patient.
All other patients received TACE. e impact of predened patient and
treatment related factors on QOL (EORTC QLQ-C30 and EORTC QLQ-
CR29) was evaluated. Primary endpoint was feasibility.
Results: Between 06/2016 and 06/2017 19 patients received TACE and 19
patients SBRT, of whom one patient dropped out during SBRT because of
lung progression. In the TACE-arm the median age was 69 years, medi-
an tumor size was 32 mm and median Child-Pugh Score (CPS) 5 points;
two patients were BCLC stage A, fourteen B and two C. Patients in the
SBRT-arm had a median of 73 years, median tumor diameter was 52 mm
and median CPS was 5 points, 9 patients were BCLC stage B and 9 C, 3
of them had a metastatic disease. A portal vein thrombosis was present
in 6 patients only in the SBRT group. Seven patients in the TACE group
received further TACEs and 1 patient a liver transplantation. In the SBRT
group 1 and 2-year overall survival rate was 56% and 74% in the TACE
group (p=0.1). e 1-year local control rate (LCR) was 90% in the SBRT
group and 70% in the TACE group (p=0.2). ere was no statistically sig-
nicant dierence in the QOL at baseline for both groups, and no dier-
ence between baseline and follow-up. One patient had a grade 5 stula in
the SBRT group and one patient had a grade 5 hepatic failure in the TACE
group, 2 a hepatic failure grade 3, 1 grade 3 pancreatitis, 1 grade 3 cholan-
gitis and one abscess in the TACE group.
Conclusions: e primary endpoint feasibility was achieved with 38 pa-
tients included during 12 months in a single center. SBRT leads to good
local control in far advanced HCC with acceptable toxicity compare with
TACE despite of more advanced disease in the SBRT group.
836
Local Radio-Ablation in Hepatic Malignancy – Esprit Study:
A Dosimetric Comparison of Interstitial HDR-Brachytherapy
(IBT) and Body Stereotaxy (SBRT)
Peter Hass 1; Thomas Brunner 1; Mathias Walke 1; Frank Meyer 2; D. Albers 3;
C. Petersen 3; F. Walter 4; Jens Ricke 5; S. Corradini 4
1Dept. of Radiation Therapy, University Hospital at Magdeburg, Magdeburg,
Deutschland
2Dept. of General, Abdominal, Vascular and Transplant Surgery, University
Hospital at Magdeburg, Magdeburg, Deutschland
3Dept. of Radiotherapy and Radiooncology, University Hospital at Hamburg-
Eppendorf, Hamburg, Deutschland
4Dept. of Radiotherapy, Ludwig-Maximilian University at Munich, Munich,
Deutschland
5Dept. of Radiology, Ludwig-Maximilian University at Munich, Munich,
Deutschland
Purpose: To statistically compare relevant dosimetric parameters for
tumor lesion and liver of the both local ablading methods such as:
interstitial HDR-brachytherapy (iBT) and
stereotactic body stereotaxy (SBRT)
in the treatment of primary and secundary liver malignomas.
Methods: 1) In this retrospective study (favored by the local ethic
committee), all patients with the characteristics mentioned above (such
as ECOG <2; oligo-metastases; maximum, 6 hepatic metastases) were
enrolled. Aer iBT, the Clinical Target Volumes (CTV = Planning Target
Volume [PTV] in brachytherapy [= iPTV]) were isotropically extended
to stereotactic PTV (sPTV) according to Scheer et al. For these sPTV,
stereotactic plans were calculated, the PTV-surrounding prescription
dosages were according to the iBT plans.
2) e “dose contraints“ for the OAR valid for iBT were strictly taken into
account during SBRT-planning. e following dosimetric parameters of
the iBT- and SBRT-plans were documented for statistical analysis: V5 of
the liver (absolute [cm3] + relative [%]), D99.9 and D90 of the PTV.
Primary end point of the study was the assessment of the dosimetric dif-
ferences between two relevant procedures of radiation therapy.
Results: From 12/2018 to 08/2009, 85 consecutive patients with 1–6 small
and 1 single large oligometastasis (n=61), respectively, or with prima-
ry hepatic tumor lesions (n=24) were enrolled. Median iPTV was 34.66
(range, 0.63–410) cm3, the calculated median sPTV was 73.24 (range,
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6.06–593) cm3, the number of the used iBT-catheters ranged from 1 to 8.
In all four parameters, there were signicant dierences between iBT and
SBRT favoring iBT.
Conclusions: iBT provides signicant advantages from a dosimetric point
of view with regard to a low liver exposure and the eective PTV dosages
D99.9 und D90 (taking into account the OAR – “dose-constraints“). In
additon, the today’s valid ICRU91 norm has not been used for the SBRT-
plan calculation yet. is will be analyzed in a further study.
Disclosure Statement: Nothing to be disclosed.
Rehabilitation and Long-term Burden in Social Medicine (Survivor)
Vorträge
165
Financial and Social Impact of Cancer in Adolescents and
Young Adults (AYA)
Mathias Freund 2; Volker König 1; Gerhard Faber 3; Ulf Seifart 4
1Klinik Bad Oexen, Bad Oeynhausen, Deutschland
2Berlin, Deutsche Stiftung für junge Erwachsene mit Krebs, Berlin, Deutschland
3Celenus Teufelsbad Fachklinik, Abteilung Onkologie, Blankenburg,
Deutschland
4Klinik Sonnenblick, Marburg, Deutschland
Purpose: 16,000 AYA cancer patients from 15 to 39 years are diagnosed
per year in Germany. More than 80% of them can be cured but the disease
and its treatment can lead to serious nancial and social consequences.
Methods: Publications on the nancial situation, employment, and return
to work in AYAs with cancer were analyzed. Data were reviewed and put
into the context of epidemiological and medical data. Furthermore ques-
tions asked in the portal “Young and Cancer” operated by the German
Foundation for Young Adults with Cancer are discussed.
Results: Cancer causes a drastic reduction in the quality of life due to
nancial impairments because employment is reduced or absent. AYA pa-
tients are heterogeneous in diagnosis, social situation and age group. Pub-
lications dierentiate oen poorly due to small numbers and unspecied
selections. Eects of dierent social security systems, legal regulations,
development of economy and labor market are not considered. In Germa-
ny nancial burdens arise in the early course of cancer by out of the pocket
payments and co-payments as well as by gaps in the nancial security in
special groups such as students. Cancer-related fatigue is a major obstacle
for full return to work but does not receive sucient scientic attention.
Long-term survivors experience discrimination trying to become public
ocers or getting housing mortgages and health insurances. Patients
questions focus on rehabilitation, stepwise reintegration into work, and
disability.
Conclusions: In Germany the data base on social and nancial conse-
quences of cancer in AYA needs to be improved. Dierentiated data
should be obtained by a population-based approach. Data from cancer
registries, social security, and health insurances have to be connected with
data on economic development and working market. Relief from out of
the pocket payments and co-payments is needed. Further steps include
improvements of social security in some groups and steps against discrim-
ination of long-term survivors.
Disclosure Statement: I disclose that I have no conicts of interest.
Poster
113
Learning Personalized Virtual Reality Avatars for
Chemotherapy-Induced Peripheral Neuropathy Rehabilitation
in Breast Cancer
Daria Kurz 1; Cristian Axenie 2
1Akademisches Lehrkrankenhaus der Ludwig-Maximilians Universität München,
Interdisziplinäres Brustzentrum, Helios Klinikum München West, München,
Deutschland
2Technische Hochschule Ingolstadt, Audi Konfuzius-Institut Ingolstadt Lab,
Ingolstadt, Deutschland
Purpose: Virtual Reality (VR) sensorimotor rehabilitation in breast can-
cer survivors is a promising non-opioid alternative to handle Chemother-
apy-Induced Peripheral Neuropathy.
Methods: CIPN has a staggering incidence of up to 60% in taxane-based
therapy, aecting as many as 83% of breast cancer patients [1]. VR reha-
bilitation is still in its infancy [2] but will soon provide digital alter-egos
of patients (avatars) and, using Machine Learning (ML), correct and com-
pensate for painful sensorimotor decits [3]. Our system [4] is a rst at-
tempt at such highly-realistic adaptive VR.
Results: Our experiments show that using ML algorithms for VR avatars
we are able to assess motion patterns and decit levels. We achieve that by
learning underlying correlations in patients motion kinematics. We show
that our system oers in average a 35% accuracy improvement in body
joint positions estimation and 83% accuracy improvement in body joint
rotation estimation over state-of-the-art. In such therapies it is assumed
that the delity of virtual to physical world movements is vital for reha-
bilitation, in order to promote the recovery of movement, balance, and
quality of life.
Conclusions: Our system provides a platform for personalized CIPN
VR-based sensorimotor rehabilitation including an ML learnt assessment
of patient motion kinematics to support clinicians to better detect CIPN
symptoms compared to relying solely on patient-reported measures.
References:
1. S. M. Monfort, et al., “Gait, balance, and patient-reported outcomes during
taxane-based chemotherapy in early-stage breast cancer patients,” Breast can-
cer research and treatment, vol. 164, no. 1, 2017.
2. V. C. Tashjian, et al., “Virtual reality for management of pain in hospitalized
patients: Results of a controlled trial,” JMIR Mental Health, vol. 4, no. 1, Mar
2017.
3. M. Schwenk, et al., “Interactive balance training integrating sensor based
visual feedback of movement performance: a pilot study in older adults,” J. of
Neuroeng. and Rehab., vol. 11, no. 1, 2014.
4. VIRTOOAIR: https://gitlab.com/akii-microlab/virtooair
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2018
342
Purdue Pegboard Test – A New Diagnostic Method for the
Assessment of Chemotherapy-Induced Polyneuropathy in
Breast Cancer Patients
Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann
Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,
Bad Elster, Deutschland
Purpose: Polyneuropathy is a common side eect of neurotoxic chemo-
therapy in breast cancer patients. Aim of this study was the evaluation of
the perdue pegboard test in diagnostics of polyneuropathy induced func-
tional decits.
Methods: 89 patients (mean age 66,4 y) suering on chemotherapy in-
duced polyneuropathy manual dexterity and bimanual coordination were
examined using Purdue pegboard test at the beginning and at the end of a
three-week inpatient rehabilitation.
Results: For the dominant [mean score 12.3 (SD 2.6) to 13.4 (SD 2.5);
eect size d=0.6] and non-dominant side [mean score 12.0 (SD 2.5) to
12.6 (SD 2.7); eect size d=0.4], the functionality during rehabilitation
was signicantly improved (p <0.001). e two-handed test [mean score
9.9 (SD 2.6) to 10.3 (SD 2.3); eect size d=0.2] showed a signicant dif-
ference only (p = 0.05). With the assembly test [mean score 22.7 (SD 7.8)
to 23.5 (SD 8.2); eect size d=0.2], no signicant dierence was found
(p = 0.154) (1).
Conclusions: Purdue pegboard test is a useful diagnostic tool in evalua-
tion and control of functional decits due to polyneuropathy.
Reference:
1. Cohen J. Statistical power analysis for the behavioral sciences Hillsdale. NJ:
Lawrence Earlbaum Associates. 1988;2.
Disclosure Statement: e authors declare that they have no conict of interest.
346
Assessment of Discharge Management in Oncological
Rehabilitation from the Perspective of Patients
Heike Kähnert 1; Harald Fischer 2; Eva-Maria Kalusche-Bontemps 3;
Birgit Leibbrand 4
1Institut für Rehabilitationsforschung, Norderney, Abteilung Bad Salzuen, Bad
Salzuen
2Klinik Rosenberg, Bad Driburg
3MediClin Klinik Reichshof, Reichshof-Eckenhagen
4Salzetalklinik, Bad Salzuen
Purpose: Rehabilitation, with its discharge management, provides ideal
conditions for long-term care for oncology patients. is study aims to
analyze rehab discharge management from the perspective of oncology
patients and to identify measures for a successful rehab discharge man-
agement.
Methods: Data collection was done by questionnaire (oncological inpa-
tients, n=377) at the end and three months aer rehabilitation and by tele-
phone interviews (n = 40) one month post-inpatient. e questionnaires
were analyzed descriptively and the interviews were evaluated by content
analysis.
Results: 48% of oncology patients report at the end of the rehab that there
was insucient guidance about aercare recommendations during rehab
and about 44% rated the aercare as less helpful. Overall, more occupa-
tional aercare recommendations were desired. ree months aer rehab,
54% of the participants gave the discharge management a marking of
good” or “very good” and 23% the grade “sucient” or worse. Approx-
imately two-thirds of the respondents felt well prepared for life at home.
For about half of the participants, however, the aercare recommenda-
tions were not sucient. Essentials of a successful discharge management
were stated: an individualized aercare, job-related support, information
or contact addresses on ‘rehab-aer-care services’ including scheduling,
cooperation between physicians and rehab-clinics and the developing of
a tele rehab-aercare.
Conclusions: In the future, the rehab-discharge management and es-
pecially the aercare recommendations should be more tailored to the
individual situation of the patient. In addition, tele-aercare should be
organized and strategies developed to promote cooperation between phy-
sicians and rehab-clinics.
Disclosure Statement: Dr. Leibbrand and Dr. Fischer are on the board of VfR e.V.,
Norderney.
350
Reliability of Muscular Strength Assessment with the Pressure
Air Biofeedback (pab®) Device in Prostate Cancer Survivors
Alexander Stäuber 1; Marc Heydenreich 2; Gerrit-René Walke 2;
Andries Pienaar 3; Dirk-Henrik Zermann 2; Henry Schulz 1
1Chemnitz University of Technology, Professorship of Sports Medicine / Sports
Biology, Chemnitz, Deutschland
2Vogtland-Klinik Bad Elster, Department of Urology & Urooncology, Bad Elster
3University of KwaZulu-Natal, Discipline of Biokinetics, Exercise and Leisure
Sciences, Durban, South Africa
Purpose: Muscular strength is a key component of rehabilitation and
a strong predictor of functional capacity. e pressure air biofeedback
(pab®)devicewas developed to be easily used in a home or clinical testing
environment for diagnosis of muscular strength and allows the measure-
ment of various muscle groups. Aim of the study was to evaluate retest-
reliability of dierent standardstrengthtests in prostate cancer survivors
(PCS) duringuro-oncologicrehabilitation.
Methods: A total of 70 PCS (64±8 yr) performed seven standardized
strength tests (SCP=sit chest press, HGS=handgrip strength, TE=triceps
extension, BC=biceps curl, SHA=standing hip abduction, KE=knee
extensionandHAD=hip adduction) with pab® in a single group 24h-test-
retest design.
Results: Repeated measures ANOVA revealed no systematic error for any
standard strength test with exception of TE test for the le arm (p<0.05).
Relative reliability (ICC 3,1) was ‘excellent’ for HGS and HAD (ICC
range>0.90), ‘good’ for SCP and TE (ICC range 0.75-0.90) and ‘moderate
for BC, SHA and KE (ICC range 0.64-0.74). e SEM% was lowest for
HGS and HAD (<10%) while the other standard tests ranged between
12-25% with the highest SEM% indicated for BC, SHA and KE (≥20%).
Conclusions: e pab® device demonstrated acceptable test-retest reli-
ability for most of the standard strength tests except the BC, SHA and KE
test. In particular, assessment of handgrip and hip adductor strength was
shown to be highly reliable. With regard to the only moderate reliable BC,
SHA and KE tests, a modication of the testing methodology is necessary
to improve the consistency and to justify its possible application in future
testing protocols.
Disclosure Statement: e authors have no relevant nancial or non-nancial
relationships to disclose.
353
Functional Status and Occurrence of Critical Prognostic Values
in Prostate Cancer Survivors in Uro-Oncological Rehabilitation
Alexander Stäuber 1; Marc Heydenreich 2; Gerrit-René Walke 2;
Dirk-Henrik Zermann 2; Henry Schulz 1
1Chemnitz University of Technology, Professorship of Sports Medicine / Sports
Biology, Chemnitz, Deutschland
2Vogtland-Klinik Bad Elster, Department of Urology & Urooncology, Bad Elster,
Deutschland
Purpose: Handgrip strength (HGS), 6-minute walk distance (6MWD)
and phase angle (pA) of bioelectrical impedance analysis (BIA) have
been shown to be strong biomarkers of functional status and powerful
predictors of mortality invarious patient groups.eaim of this study
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was to nd out how oen prostate cancer survivors (PCS) demonstrate
HGS, pA and 6MWD below predicted [1] or critical cuto values [2,3]
prior and post a 3-weekuro-oncologicalrehabilitationprogram.
Methods: 125 PCS (66±7 yr) were examined at the beginning (T1) and
the end (T2) oftherehabilitation program. Standardized assessment
included a handgrip strength test following the Southampton protocol
withahydraulic hand dynamometer (Baseline®, HIResTM, Gauge ERTM,
USA), 6-minute-walk-test (6MWT) and BIA (BIA® 3 SF, EgoFit GmbH,
Germany).
Results: At T1,39.2% of PCS presented a critical HGS below individual
cuto which changed to 26.4% at T2. In 20.8%of PCSa critical pA was
detected at T1 with no change of incidence at T2. A 6MWD lower than the
individual predicted value was found in 67.2% of PCA at T1 and in 33.6%
cases at T2. Between T1 and T2 signicant improvements were obtained
for HGS andthe6MWD (HGS:Cohens d=0.5; 6MWD: d=1.1; p<0.001)
but not for pA (T1: 5.2±0.8°; T2: 5.2±0.7°).
Conclusions: e data provides knowledge about the occurrence of crit-
ical prognostic values of functional status in PCS in theuro-oncologi-
calrehabilitation setting. Moreover, data has shown that a 3-week reha-
bilitation program is eective in improving strength and endurance but
without aecting the pA. e routine assessment of HGS, 6MWDand pA
may give the option to conduct a risk stratication for PCS which could
aect the ongoing process of survivorship care.
References:
1. Enright & Sherrill: Am J Respir Crit Care Med 1998
2. Steiber: PLoS One 2016
3. Norman et al: Am J Clin Nutr 2010
Disclosure Statement: e authors have no relevant nancial or non-nancial
relationships to disclose.
355
Domain-Specic Consideration of the FACT-P inGerman
Prostate Cancer Survivors before and afterUro-Oncological
Rehabilitation
Alexander Stäuber 1; Marc Heydenreich 2; Gerrit-René Walke 2;
Dirk-Henrik Zermann 2; Henry Schulz 1
1Chemnitz University of Technology, Professorship of Sports Medicine / Sports
Biology, Chemnitz, Deutschland
2Vogtland-Klinik Bad Elster, Department of Urology & Urooncology, Bad Elster,
Deutschland
Purpose: Many of the treatments for prostate cancer adversely aect
health-related quality of life (HRQoL).HRQoL in prostate cancer survi-
vors is measurable bythe internationally most commonly used FACT-P
instrument which comprises the ve domainsof‘physical’, ‘social/family’,
emotional, ‘functional‘well-being and ‘additional concerns’ (consisting of
items relating specically to prostate cancer and/or its treatment).eaim
of the study was to nd out to what extent a 3-weekuro-oncologicalreha-
bilitationprogramaects the dierent HRQoL domains.
Methods: 128 men (66±7ys) completedtheFACT-P (version 4)prior
and post the rehabilitation program. Dierences were tested for statisti-
cal signicance by Wilcoxonrank sumtest. Eect size (r) was derivedby
dividing the absolute standardized test statistic z by the square root of the
number of pairs. Based on the guideline given by Cohen [1],r = 0.3 was
considered to be a medium and r=0.5 a large eect size.
Results: Statistical analysis revealed signicant improvements with me-
dium eect sizes for all HRQoL domains (p<0.001, r=0.3-0.4) with the
exception of the ‘social/family’ domain (p>0.05). FACT-P total score also
increased signicantly (p<0.001, r=0.5).
Conclusions: Measuring and identifying issues of HRQoL in the pros-
tate cancer survivor may create an opportunity to discuss disease-specic
problems andexchangeinformation transfer from health professional to
patient and vice versa.Uro-oncologicalrehabilitation is very eective in
improving HRQoL and should be oered to all prostate cancer survivors.
References:
1. Cohen: Psychol Bull 1992
Disclosure Statement: e authors have no relevant nancial or non-nancial
relationships to disclose.
356
Body Balance after Cancer Therapy – The Role of Patients Age?
Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann
Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,
Bad Elster, Deutschland
Purpose: Cancer and cancer therapies (surgery, RT, CT) have a negative
impact on physical and mental well-being. e task of rehabilitation is
overcoming side eects and regaining good quality of life. Physical train-
ing was proven to be very eective (1). e aim of the present prospective
study was to evaluate the eciency of a 3-week rehabilitation program on
the sense of balance in dependence of patient age.
Methods: 89 patients (Ø 62 Jahre) aer cancer therapy were examined. At
the beginning and at the end of a 3-week rehabilitation program a Micros-
wing Balance Test (sense of balance) was performed.
Results: e following results (pre-post-comparison) were obtained.
e stability of the right side in patients under the age of 49 years (n=9)
improved from an average of 67.4% (12.8) to 76.1% (9.2) (p=0.03), be-
tween 50-59 years (n=23) from 62.0% (13.8) to 67.0% (11.6) (p=0.02),
between 60-69 years (n=36) from 54.7% (19.9) to 64.7% (14.2) (p=0.001)
and over the age of 70 years (n=21) from 39.4% (19.7) to 45.0% (20.3)
(p=0.05).
e stability of the le side in patients under the age of 49 years (n=9)
improved from an average of 71.1% (8.4) to 75.9% (6.8) (p=0.02), between
50-59 years (n=23) from 64.4% (16.0) to 69.2% (10.6) (p=0.03), between
60-69 years (n=36) from 55.6% (16.0) to 64.6% (11.8) (p=0.001) and over
the age of 70 years (n=21) from 44.2% (19.1) to 50.4% (18.3) (p=0.005).
Conclusions: A signicant improvement of the sense of balance could be
demonstrated in all age groups. Functional training therapy to promote
endurance, coordination and strength contributes improving physical
function and performance. Patient of all age groups benet form special-
ized oncological rehabilitation.
Reference:
1. Zopf E, Baumann F, Pfeifer K. Körperliche Aktivität und körperliches
Training in der Rehabilitation einer Krebserkrankung. Die Rehabilitation
2014;53(01):2-7.
Disclosure Statement: e authors declare that they have no conict of interest.
357
1H- And 24-Hour Pad Test for Incontinence Diagnostics after
Prostate Cancer Surgery - Assessment of the “Minimal Clinical
Important Dierence” (MCID) and Test-Retest Reliability
Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann
Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,
Bad Elster, Deutschland
Purpose: e 1- (1hPT) and 24-h Pad Test (24hPT) are used as objective
diagnostic methods for the assessment of postprostatectomy stress uri-
nary incontinence. e aim of this study was to determine the “minimal
clinical important dierence” (MCID) and the test-retest reliability of the
1hPT and 24hPT.
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Methods: 93 patients (mean age 64.0 years) were examined performing a
1hPT and 24hPT at the beginning and at the end of a three-week inpatient
rehabilitation. e Pearson correlation was used for the statistical evalua-
tion of the retest reliability. Values from 0.7 indicate a good repeatability
of the test. e MCID was determined using distribution-based methods
(intra-class coecient (ICC), standard error of the mean (SEM), half stan-
dard deviation (0.5 SD).
Results: e data of all 93 patients could be evaluated. e average urine
loss improved for 1hPT from 22.6g (31.2) to 8.5g (13.2) (p<0.001) and for
24hPT from 242.9g (269.6) to 126.7g (171.1) (p<0.001) before and aer 21
days of rehabilitation. e test-retest reliability resulted in a value of 0.85
for the 1hPT and a value of 0.88 for the 24hPT. e standard error of the
mean was for 1hPT 9.5 and for 24hPT 82.1. e half standard deviation
was for 1hPT 12.6 and for 24hPT 85.7.
Conclusions: e results show that the 1hPT and the 24hPT have a very
good test-retest reliability in everyday clinical practice. e minimum
clinical dierence (MCID) for urine loss reduction that is considered to
be signicant is between 9.5g to 12.6g for the 1hPT and between 82.1g to
85.7g for the 24hPT.
Disclosure Statement: e authors declare that they have no conict of interest.
358
Improvement of Coordination Skills by a Specic
Sensorimotor Training as Part of Oncological Rehabilitation
Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann
Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,
Bad Elster, Deutschland
Purpose: e combination of classical continence training with oscilla-
tion rod training is an established concept in the rehabilitation of patients
with post-prostatectomy incontinence (1). e aim of this study was to
gure out if the sensorimotor training using an oscillating rod, originally
used for incontinence therapy, also has a positive inuence on the sense
of balance and the reaction time in patients aer radical prostatectomy.
Methods: 47 patients (Ø 64.3 years) aer radical prostatectomy were ex-
amined. All study participants completed a standard therapy program,
consisting of classical continence training, sensorimotor training, endur-
ance training and a moderate strength training. e sense of balance and
the reaction time were measured using Microswing Balance Test (MBT)
and Trac Light Test (TLT) at the beginning and at the end of rehabilita-
tion. e urinary incontinence was evaluated with the 1-h and 24-h test
pad.
Results: e following results (pre-post-comparison) were obtained:
1. highly signicant improvement of postural stability (p<0.001)
stability right side from 51% to 57%
stability le side from 53% to 59%
overall stability from 52% to 58%
2. highly signicant improvement in reaction time, by Ø 12 milliseconds
(p<0.001)
3. signicant improvement of 1-hour pad test (21.2g auf 9.4g (p<0.05))
4. highly signicant improvement of 24-hour pad test (218.1g auf 135.1g
(p<0.001))
Conclusions: A signicant improvement of the sense of balance and the
reaction time was shown. erefore, could be concluded, that not only
the continence apparatus but also the local and deep back and abdominal
muscles as well as the sensory control of the arms, legs and stabilization of
the trunk benet from oscillation rod therapy.
Reference:
1. Heydenreich M, Puta C, Gabriel H, Zermann D, Oscillating pole treatment-a
new eective treatment option for postprostatectomy urinary incontinence.
Oncology Research and Treatment; 2016.
Disclosure Statement: e authors declare that they have no conict of interest.
359
Clinical Eects of Function-Oriented Rehabilitation on Hand
Strength after Cancer Therapy?
Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann
Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,
Bad Elster, Deutschland
Purpose: Improving physical performance is one of the important expec-
tations on uro-oncological rehabilitation. Aim of this study was the eval-
uation of the handgrip strength with a hand dynamometer for diagnostic
during oncological rehabilitation. A comparison with normative reference
values (NRV) was performed.
Methods: 109 patients (mean age 66.8 y) were examined performing
a handgrip strength measurement at the beginning and at the end of a
three-week inpatient rehabilitation. Rehabilitation program included en-
durance, moderate strength and functional training.
Results: e following results (pre-post-comparison) were obtained.
1. signicant improvement of handgrip strength (37.9 kg (8.7) to 40.4 kg
(9.4); p < 0,001)
2. signicant improvement of handgrip strength in patients
between 40-60 years (n=20) from 41.5 kg (7.9) to 44.7 kg (8.7)
(p = 0.003; NRV=49.7 (2.4))
between 61-70 years (n=53) from 39.0 kg (8.5) to 41.8 kg (9.1)
(p<0.001; NRV=46.1 (2.7))
between 71-90 years (n=36) from 34.3 kg (8.3) to 37.6 kg (9.4)
(p<0.001; NRV=39.8 (3.0))
Conclusions: Handgrip strength is a useful diagnostic tool in evaluation
of general health improvements due to oncological rehabilitation. A sig-
nicant increase of handgrip strength was shown however norm values
are not achieved (1). erefore, an appropriate training as learned during
rehabilitation should be continued aer nishing inpatient rehabilitation
as a home training program.
Reference:
1. Steiber N. Strong or weak handgrip? Normative reference values for the
German population across the life course stratied by sex, age, and body
height. PloS one. 2016;11(10):e0163917.
Disclosure Statement: e authors declare that they have no conict of interest.
364
Manual Dysfunction after Breast Cancer Treatment - Inuence
of Specialized Sensorimotor Rehabilitation
Gerrit-René Walke; Marc Heydenreich; Dirk-Henrik Zermann
Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,
Bad Elster, Deutschland
Purpose: Around one third of chemotherapy patients develop a neu-
ropathy aer their treatment. Even patients without chemotherapy have
problems in their ne motor skills. e purpose of this study was to nd
out if breast cancer patients with and without chemotherapy benet of a
3-week-rehabilitation program with focus on ne motor skills in occupa-
tional therapy
Methods: 162 patients (Ø 60 years) aer complex breast cancer treatment
were evaluated, 89 patients with chemotherapy and 73 without chemo-
therapy. All patients completed successfully a 3-week-rehabilitation pro-
gram. is included occupational therapy (hand baths, design therapy),
physiotherapy (cell baths, coordinative exercises) and sports therapy (os-
cillation rod therapy). Study diagnostics included a Purdue Pegboard Test
(PPT) for evaluation of manual dysfunctions and the small ber neuropa-
thy screening list (SFNSL) for sensory and pain diagnostics (1, 2).
Results: e following results were obtained:
All patients achieved following results
PPT – dominant hand (13.1 to 13.8; p<0.001)
PPT – non dominant hand (12.5 to 13.2; p<0.001)
SFNSL (18.6 to 16.3; p<0.001)
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Patients with chemotherapy
PPT – dominant hand (12.6 to 13.8; p<0.001)
PPT – non dominant hand (12.3 to 13.0; p=0.008)
SFNSL (21.2 to 18.3; p<0.001)
Patients without chemotherapy
PPT – dominant hand (13.6 to 13.8; p=0.274)
PPT – non dominant hand (12.8 to 13.4; p=0.003)
SFNSL (15.5 to 13.6; p=0.006)
Conclusions: A specialized rehabilitation program aer breast cancer
therapy allows the improvement of manual decits and neuropathic
symptoms. Especially chemotherapy patients with polyneuropathy benet
from occupational therapy.
References:
1. Hoitsma E, De Vries J, Drent M. e small ber neuropathy screening list:
construction and cross-validation in sarcoidosis. Respiratory medicine.
2011;105(1):95-100.
2. Tin J, Asher EJ. e Purdue Pegboard: norms and studies of reliability and
validity. Journal of applied psychology. 1948;32(3):234.
Disclosure Statement: e authors declare that they have no conict of interest.
368
Body Balance, Reaction Time and Handgrip Strength in
Incontinent and Continent Patients after Prostatectomy
Gerrit-René Walke; Marc Heydenreich; Dirk-Henrik Zermann
Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,
Bad Elster, Deutschland
Purpose: Stress urinary incontinence is one of the side eects aer radical
prostatectomy. e identication of inuencing factors for post-prosta-
tectomy urinary incontinence is of great interest. e purpose of this pilot
study was to gure out if the pre-existing body balance and the muscular
situation prior to therapy have an impact on the continence situation aer
surgery.
Methods: 20 incontinent (1h pad test > 50g) and 20 continent (1h pad
test < 1g) patients were examined. Study diagnostics included 1-h-PAD-
Test, Microswing Balance Test (Posturo Kybernetik Test – PKT), a hand
strength dynamometer test and a Sta-drop test (reaction time test).
Results:
1. Incontinent patients have an inferior body balance then continent pa-
tients by trend (39.26% to 44.85%; p=0.349)
2. Incontinent patients have a longer reaction time than continent pa-
tients by trend (18cm to 16.51 p=0.34)
3. Continent patients have a better muscular situation by trend (50kg to
45kg; p=0.06)
Conclusions: e results show that there are dierences between conti-
nent and incontinent patients aer prostatectomy relating to body bal-
ance, muscular strength and reactivity (common health condition) prior
to surgery. Pelvic oor function and trunk stability are inuenced by the
existing body balance of the patients. erefore, a holistic, sensorimotor
(oscillation rod treatment (1)) and functional (continence training) reha-
bilitation program is needed.
Reference:
1. Heydenreich M, Puta C, Gabriel H, Zermann D. Oscillating pole treatment-a
new eective treatment option for postprostatectomy urinary incontinence.
Oncology Research and Treatment; 2016.
Disclosure Statement: e authors declare that they have no conict of interest.
597
Targets for the Prevention of Suicidality in Long-Term
Childhood Cancer Survivors
Mareike Ernst 1; Elmar Brähler 1; Philipp S. Wild 2; Claus Jünger 2; Jörg
Faber 3; Astrid Schneider 4; Manfred E. Beutel 1
1Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik
und Poliklinik für Psychosomatische Medizin und Psychotherapie, Mainz,
Deutschland
2Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Präventive
Kardiologie und Medizinische Prävention, Mainz, Deutschland
3Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum
für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie /
Hämostaseologie, Mainz, Deutschland
4Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Institut
für Medizinische Biometrie, Epidemiologie und Informatik (IMBEI), Mainz,
Deutschland
Purpose: Long-term childhood cancer survivors (CCS) are a vulnerable,
understudied population group. ey are at risk for physical and psycho-
social late eects of the disease and its treatment. Previous research has
also attested to elevated rates of suicidal ideation (SI) in CCS, an espe-
cially dangerous indicator of distress. However, there is little knowledge
about potential risk factors which could inform screening and prevention
eorts.
Methods: A register-based sample of 916 adult long-term CCS was
drawn from the oldest German cohort (Mage = 34.58 years [SD = 5.53],
Mage at diagnosis = 6.15 years [SD = 4.28]). Participants underwent medical
assessments and lled out questionnaires. We conducted a linear
regression analysis on current SI, testing predictors of dierent areas:
sociodemographic, social, cancer-related, physical health and health
behavior, and psychological history as well as current distress symptoms.
Results: SI was reported by 73 CCS (8.0%). Besides a CNS tumor diag-
nosis, which was a risk factor, relevant predictors belonged to the social
and psychological domain, comprising previous suicide attempts as well
as current distress (loneliness, anxiety symptoms, depression symptoms,
social phobia symptoms). Living together with a partner was protective.
Conclusions: Decades aer having survived cancer, a subgroup of CCS is
aected by (recurrent) suicidality. CCS’ risk for SI was shaped by individ-
ual medical and psychological history, and by the current social environ-
ment and psychological comorbidities. ere is a need for more screening
eorts, e.g. in primary care settings which take account of these factors.
Interventions reducing CCS’ risk of suicide should target the social do-
main and counteract current stressors.
Disclosure Statement: CVSS is funded by the German Research Foundation
(DFG) (SP 1381/2-1&2, FA 1038/2-1&2,WI 3881/2-1&2). P.S.W. is funded by the
Federal Ministry of Education and Research (BMBF 01EO1503). PSYNA is funded
by the German Cancer Aid (DKH, 70112165 & 70113623). ere is no conict of
interest.
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2018
Sarcoma
Poster
169
Core Needle Biopsy is Superior to Incisional Biopsy for
Dierentiation of Soft Tissue Sarcomas: A Systematic Review
and Meta-Analaysis
Emrullah Birgin 1; Cui Yang 1; Svetlana Hetjens 2; Christoph Reissfelder 1;
Peter Hohenberger 1; Nuh N. Rahbari 1
1Universitätsmedizin Mannheim, Chirurgische Klinik, Mannheim, Deutschland
2Universitätsmedizin Mannheim, Abteilung für Medizinische Statistik,
Mannheim, Deutschland
Purpose: Incisional biopsies (IB) has long been considered the gold stan-
dard for diagnosis of so tissue sarcomas (STS) although there is substan-
tial evidence that core needle biopsy (CNB) oers an adequate alternative
technique with less invasiveness and costs. We conducted a meta-analysis
to compare the diagnostic accuracy of both biopsy techniques in STS with
reference to the nal histopathological result.
Methods: A systematic review of literature in the MEDLINE and EM-
BASE databases was performed. Pooled estimates of thediagnosticaccu-
racywere calculated using random eects modeling. Study quality was
assessed by using the QUADAS-2 checklist.
Results: 17 eligible studies (2680 patients with 1582 CNB and 241 IB)
were included. CNB detected correct dignity of lesions with a pooled sen-
sitivity and specicity of 97% (95%CI: 95-98%) and 99% (95%CI: 97-99%)
compared to IB with a pooled sensitivity and specicity of 96% (95%CI:
92-99%) and 100% (95%CI: 94-100%), respectively. Estimated summary
diagnostic accuracy to detect correct STS histotype were as following:
CNB sensitivity 88% (95%CI: 86-90%) and CNB specicity 77% (95%CI:
72-81%) versus IB sensitivity 93% (95%CI: 87-97%) and IB specicity
65% (95%CI: 49-78%). Complications following CNB were signicantly
reduced compared to IB (RR 0.14; 95% CI 0.03 – 0.56; P=<0.01; I2=0%).
e quality of included studies revealed a high risk of bias.
Conclusions: CNB is the superior method to dierentiate STS subtype
with lower complication compared to IB.
Reference:
1. Mehren Mv, Randall RL, Benjamin RS, et al. So Tissue Sarcoma, Version
2.2018, NCCN Clinical Practice Guidelines in Oncology. 2018;16(5):536.
Disclosure Statement: None of the authors have any conicts or nancial support
to disclose.
203
Ewing Sarcoma as Secondary Malignancy in a Heterogeneous
Group of Cancer Patients
Katja Kauertz 1; Heribert Jürgens 2; Michael Paulussen 3; Uta Dirksen 1;
Andreas Ranft 1
1University Hospital Essen, Pediatrics III, Hematology/ Oncology, West German
Cancer Center and German Cancer Research Center, Essen, Deutschland
2University Hospital Muenster, Pediatrics, Hematology/Oncology, Münster,
Deutschland
3Witten/Herdecke University, Children’s Hospital, Pediatrics, Hematology/
Oncology, Datteln, Deutschland
Purpose: Ewing sarcoma (EWS) is the second most frequent bone asso-
ciated tumor in children, adolescents and young adults [1]. Standard of
care is comprised of intensive polychemotherapy, local surgery and radio-
therapy [2]. Among patients with this rare malignancy, secondary EWS
accounts for a small minority of all cases and data regarding EWS as a
secondary malignancy are limited.
Methods: From 1991-2009, two consecutive and nationwide Ewing sarco-
ma trials enrolled 2422 patients. e GPOH database of these two studies
was analyzed for EWS as a secondary malignancy. Kaplan Meier method
was used to estimate event-free survival (EFS) and overall survival (OS).
Results: Among the 2422 patients enrolled in the EICESS 92 and EURO-
EWING 99 studies, 26 cases of secondary EWS were reported. Median
time of follow-up was 3.6 years (range 0.3-14.6) Median age at diagnosis
of secondary EWS was 16.5 years (range 6.7-59.8) compared to 6.4 (range
0.8-53.5) at diagnosis of primary malignancy. Localized Ewing sarcoma
occurred in 15 cases (58%), whereas 11 (42%) patients suered from
metastatic disease. A heterogeneous group of malignancies preceded
secondary EWS; most common primary malignancies included acute
lymphoblastic leukemias (6), lymphomas (5), osteosarcomas (2), and
retinoblastomas (2). ree-year EFS was 0.67 (SE=0.12) for patients with
localized and 0.09 (SE =0.09) for those with metastatic disease. e 3-year
OS was 0.80 (SE=0.10) for patients with localized and 0.18 (SE=0.12) for
patients with metastatic disease.
Conclusions: As a secondary malignancy, EWS accounts for approx-
imately 1% of all reported EWS-cases. e most common hematologic
malignancies within these age groups are consistent with those that pre-
cede secondary EWS. Patient characteristics are comparable to patients
presenting with EWS as a primary malignancy.
References:
1. Grunewald, T.G.P., et al., Ewing sarcoma. Nat Rev Dis Primers, 2018. 4(1): p. 5.
2. Gaspar, N., et al., Ewing Sarcoma: Current Management and Future Approaches
rough Collaboration. J Clin Oncol, 2015. 33(27): p. 3036-46.
307
Impact of Surgical Margins in Patients with Soft Tissue
Sarcomas of the Hand
Mehran Dadras 1; Hans-Ulrich Steinau 1, 2; Ole Goertz 1, 3; Marcus
Lehnhardt 1; Björn Behr 1; Kamran Harati 1
1Klinik für Plastische Chirurgie, Berufsgenossenschaftliches Universitätsklinikum
Bergmannsheil, Bochum, Deutschland
2Sektion Sarkomchirurgie, Klinik für Allgemein-, Viszeral- und
Transplantationschirurgie, Universitätsklinikum Essen, Westdeutsches
Tumorzentrum (WTZ), Essen, Deutschland
3Klinik für Plastische Chirurgie, Martin-Luther-Krankenhaus, Berlin, Deutschland
Purpose: e hand represents a rare but surgically challenging anatomical
location of so tissue sarcomas (STS). Maintaining the surgical aim of
wide resection leads to a high rate of amputations and functional impair-
ment while impact of resection margins on survival in distal extremity
STS remains controversial. We aimed to perform a single institution anal-
ysis of long term results of hand STS to identify prognostic factors.
Methods: All patients operated for localized STS of the hand at our insti-
tution were identied. Uni- and multivariate analysis of factors associated
with 5-year local recurrence free survival (5Y-LRFS), metastases free sur-
vival (5Y-MFS) and disease specic survival (5Y-DSS) were performed.
Results: 51 patients could be identied. Of these 3 received amputations
of single ngers/nger rays while the rest could be treated without any
amputation and marginal resections in the majority of cases and positive
margins in 10% of cases. Aer a median follow-up of 77 months, 5Y-LRFS,
5Y-MFS and 5Y-DSS were 65%, 86% and 91% respectively. Tumor size was
a predictor of all three outcome parameters but positive resection margins
adversely aected LRFS only. Survival outcome was excellent and not in-
ferior to other studies on hand STS with a more radical surgical approach.
Conclusions: Conservative surgical treatment of hand STS with marginal
resection and adjuvant radiation therapy in case of high-grade STS is a
viable treatment strategy leading to a better hand preservation than more
radical surgical approaches at the cost of worse local control but not worse
survival.
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2018
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2018
331
Oncologic Impact of Wound Complications in Extremity Soft
Tissue Sarcomas
Mehran Dadras; Pascal Koepp; Christoph Wallner;
Johannes M. Wagner; Alexander Sogorski; Marcus Lehnhardt;
Kamran Harati; Björn Behr
Klinik für Plastische Chirurgie, Berufsgenossenschaftliches Universitätsklinikum
Bergmannsheil, Bochum, Deutschland
Purpose: In various malignancies, complications correlate with dimin-
ished prognosis, however literature on so tissue sarcomas is limited and
inconclusive. e aim of this study was to assess risk factors and the on-
cologic impact of wound complications in primary extremity so-tissue
sarcomas.
Methods: Patients with primary extremity so tissue sarcomas without
dissemination and with clear surgical margins (R0) were analyzed. Groups
with and without wound complications were compared by univariate and
multivariate analysis to identify risk factors. Uni- and multivariate analy-
sis of factors associated with 5-year local recurrence free survival (LRFS),
metastases free survival (MFS) and disease specic survival (DSS) were
performed.
Results: 682 patients were included in the study, wound complications oc-
curred in 94 patients (13.7%) within 90 days. Age, ASA-stage, high tumor
size and grade, tumor location in the foot, neoadjuvant radiation therapy
and operation time represented independent risk factors for wound com-
plications. Patients with wound complications had a signicantly worse
estimated 5-year LRFS of 43.9±6.4% versus 77.1±2.1%. Wound complica-
tions could be identied as a strong independent risk factor for LRFS (HR
3.02[CI 2.03-4.49], p<0.001). 5-year MFS and 5-year DSS were signi-
cantly lower for patients with wound complications in univariate analysis
but wound complications were not signicant in multivariate analysis for
MFS or DSS.
Conclusions: Wound complications aer so tissue sarcomas of the ex-
tremities are associated with worse local oncological outcome. Patients
with high risk of wound complications should be identied and strategies
implemented to reduce surgical complications and possibly improve on-
cologic prognosis.
388
Undierentiated Pleomorphic Sarcomas of the Extremities:
A Single-Institutional Analysis of 179 Patients
Kamran Harati; Ole Goertz; Andreas Pieper; Mehran Dadras;
Björn Behr; Marcus Lehnhardt
BG Universitätsklinikum Bergmannsheil, Plastische Chirurgie, Bochum,
Deutschland
Purpose: Undierentiated pleomorphic sarcoma (UPS) are a frequent
subtype within the heterogenous group of so tissue sarcomas and mostly
occur within the extremities. Surgical resection with negative margins has
been the mainstay of therapy. However, attainment of negative margins in
the extremities can be complicate due to functional important structures.
e aim of this study was to identify prognostic factors in patients with
UPS of the extremities.
Methods: We retrospectively determined the relationship between lo-
cal recurrence-free survival (LRFS), overall survival (OS) and potential
prognostic factors in 179 patients with UPS of the extremities who were
suitable for surgical treatment in curative intent. e median follow-up
time was 4.8 years.
Results: e 5-year local recurrence-free (LRFS) and overall survival
(OS) rate were 58.0% and 73.6%. Negative margin status was associated
with signicantly better LRFS and OS. e rates of LRFS and OS aer 2
years were 75.5% and 87.0% in patients with R0-resected primary tumors
and 60.0% and 75.0% in patients with R1/R2-status (LRFS: P=0.015; OS:
P=0.001). Adjuvant radiotherapy signicantly improved LRFS (5-year:
67.6% vs. 45.7%; P<0.001) and OS (5-year: 82.8 vs. 60.2; P=0.007). Both,
negative margins and adjuvant radiotherapy were found to be indepen-
dent prognostic factors in multivariate analysis.
Conclusions: e data from this study could underscore the benecial
prognostic impact of negative margins on LRFS and OS. However, the
width of negative margins seemed to be not relevant. Notably, adjuvant
radiotherapy was not only able to decrease the risk of local failure but also
improved OS in a signicant manner.
Disclosure Statement: All authors declare that they have no conict of interest.
576
Management of Patients with Gynecological Sarcoma - A
Survey among Gynecologists within the Framework of the
German Registry of Gynecological Sarcoma (REGSA)
Robert Armbrust 1; Philipp Harter 2; Cosima Brucker 3; Hans Georg Strauss 4;
Alexander Mustea 5; Michaela Bossart 6; Mustafa Zelal Muallem 1;
Julia Jordan 7; Jalid Sehouli 1
1Charite University Medicine, Gynaecological Department, Berlin, Deutschland
2Kliniken Essen Mitte, Gynaecological Department, Essen, Deutschland
3Klinikum Nürnberg, Gynaecological Department, Nürnberg, Deutschland
4University Medicine Halle, Gynaecological Department, Halle (Saale),
Deutschland
5University Medicine Bonn, Gynaecological Department, Bonn, Deutschland
6University Medicine Freiburg, Gynaecological Department, Freiburg,
Deutschland
7NOGGO e.V., Studienbüro, Berlin, Deutschland
Trials in Progress:
Prospective Registry of Gynecological Sarcoma:
Management of patients with gynecological sarcoma - a survey among
gynecologists within the framework of the German Registry of Gyne-
cological Sarcoma (REGSA)
Authors: R Armbrust, P Harter, S Brucker, H Strauß, A Mustea, M
Bossart, M Z Muallem, J Jordan, J Sehouli
Purpose: Gynecological sarcoma (GS) are rare neoplasms that make up
1% of all gynecological malignancies. ere is a high clinical and scientic
need to improve the clinical outcome. Specic data of the clinical manage-
ment, including diagnostics, surgery and medical interventions are very
limited.
REGSA is the largest prospective gynecological registry for sarcoma
in Germany. e aim of the register has been to prospectively collect data
of patients with GSs to describe their course of disease, diagnostics and
therapies.
Methods: An electronic case report was designed to register clinical data
from patients with gynecological sarcomas such as disease, surgery, ther-
apy and success of therapy aer informed consent. Additionally, the in-
formation about clinical management as stated by the participating phy-
sicians has also been recorded. is information is completed once per
study site.
e evaluation of the register data is exploratory and descriptive.
ere will be a descriptive analysis of the forms of therapy according to
the dierent types of gynecological sarcoma and their outcome. e REG-
SA study is registered on German Register of Clinical Trials (DRKS) with
the number DRKS00009240.
Results: Patient recruitment started in September 2015 and currently is
still ongoing. Up to date, 125 German study sites together with one Aus-
trian site and one Swiss site have already enrolled 500 patients (status ob-
tained on: 07/2019).
Conclusions: e result of the study might help to initiate multicenter tri-
als and to improve the standard of care. Beside the collection of all medical
data, the experiences and the treatment preferences of the physician are
analyzed by a structured interview.
Disclosure Statement: no conict of interest exists.
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613
Role of Histone Variants in Sarcoma Pathogenesis
Farina Borken 1; Chen-Jen Hsu 1, 2; Tina Maria Schnöder 1, 2;
Evgeniya Denisova 3;Prya Chudasama 3; Stefan Fröhling 3;
Claudia Scholl 3, 4; Marcus Buschbeck 5; Florian Heidel 1, 2
1Universitätsklinikum Jena, Innere Medizin II, Hämatologie und Onkologie, Jena,
Deutschland
2Leibniz-Institut für Alternsforschung - Fritz-Lipmann- Institut e.V., Jena,
Deutschland
3Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland
4Deutsches Krebsforschungszentrum, Heidelberg, Deutschland
5Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Germans Trias I
Pujol , Badalona, Spanien
Purpose: Recent studies on tumor cells have suggested that altered epi-
genetic proles including histone variants play a key role in modulating
the functional potential at dierent stages of malignant transformation
(Buschbeck et al. 2017). Multiple variants of the standard histones are en-
coded from a set of ‘orphan genes’ e.g. H2A.Z, H2A.X and macroH2A for
H2 and specically expression of H2A variants has been described in so
tissue sarcoma (STS) (Takahashi et al. 2014). Here we aim to investigate
the role of H2A histone variants in sarcoma pathogenesis.
Methods: Expression of histone variants in 372 human STS samples was
investigated by RNA-sequencing. Functional impact was investigated by
RNAi and validated by CRISPR-Cas9 mediated knockout. Proliferation,
cell cycle and viability of human STS-cell lines were analyzed by ow cy-
tometry and cellular imaging.
Results: When analyzing expression of histone variants in global
transcriptome analyses we found H2AFX, H2AFY and H2AFZ to be
highly expressed in various STS subtypes. To assess for potential functional
dependencies, we genetically inactivated H2AFX, H2AFY and H2AFZ in
a RNAi-based dropout screen in vitro using the human STS-cell line T778.
In this set of experiments especially H2AFX-depleted cells were repeatedly
outcompeted by non-infected cells. ese results could be conrmed by
knockout of H2AFX using the CRISPR-Cas9 system. Interestingly, loss
of competitive advantage was mainly caused by decreased proliferation
(n = 3, p0.044*) but did not result in higher rates of apoptosis, eects
that could be recapitulated in other STS cell lines such as MLS-402-91
(n = 3, p0.002**) and Fuji (n = 3, p0.045*).
Conclusions: In Summary our ndings provide rst evidence for a role
of H2A histone variants in STS biology. Besides dierential expression in
dierent subtypes of sarcoma, specically H2AFX appears to be relevant
for maintenance of cellular competition and proliferation in vitro.
References:
1. Buschbeck M et al. Nat Rev Mol Cell Biol. 2017 May;18(5):299-314
2. Takahashi A et al. PLoS One. 2014 Sep 4;9(9):e106801.
673
A Randomized Phase II Study of Durvalumab and
Tremelimumab Compared to Doxorubicin in Patients with
Advanced or Metastatic Soft Tissue Sarcoma (Medisarc,
AIO-STS-0415)
Viktor Grünwald 1; Philipp Ivanyi 2; Barbara Hermes 3; Armin Tuchscherer 4;
Daniel Pink 5; Sebastian Bauer 1; Lars Lindner 6; Marinela Augustin 7;
Andreas Block 8; Stephan Richter 9; Peter Reichardt 10; Martina Crysandt 11;
Annette Hipper 12; Marc Fischer 12
1Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Essen, Deutschland
2Medizinische Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie,
Onkologie und Stammzelltransplantation, Hannover, Deutschland
3Medizinische Universitätsklinik Tübingen, Klinik für Innere Medizin VIII,
Tübingen, Deutschland
4Universität zu Köln, Klinik I für Innere Medizin, Centrum für Integrierte
Onkologie Aachen Bonn Köln Düsseldorf, Köln, Deutschland
5HELIOS Klinikum Bad Saarow, Sarkomzentrum Berlin-Brandenburg, Klinik für
Hämatologie, Onkologie und Palliativmedizin, Bad Saarow, Deutschland
6Klinikum der Universität LMU München, Medizinische Klinik und Poliklinik III,
München, Deutschland
7Universitätsklinik der Paracelsus Medizinischen Privatuniversität Klinikum
Nürnberg, Medizinischen Klinik 5, Hämatologie und Onkologie, Palliativmedizin,
Nürnberg, Deutschland
8Universitätsklinikum Hamburg Eppendorf, Onkologisches Zentrum, II.
Medizinische Klinik und Poliklinik, Hamburg, Deutschland
9Universitätsklinikum Carl Gustav Carus Dresden, University Cancer Center/
Medizinische Klinik I, Dresden, Deutschland
10HELIOS Klinikum Berlin-Buch, Sarkomzentrum Berlin-Brandenburg, Onkologie
und Palliativmedizin, Berlin, Deutschland
11Universitätsklinik RWTH Aachen, Klinik für Hämatologie, Onkologie,
Hämastaseologie und Stammzelltransplantation, Aachen, Deutschland
12AIO-Studien-gGmbH, Berlin, Deutschland
Purpose: So tissue sarcomas (STS) are rare tumors and exhibit sub-
stantial histological diversity. Ecacious targeted 1st line treatment for
advanced/metastatic STS is not available, and the standard therapy has
been anthracycline-based for decades. is strategy shows poor ecacy,
as demonstrated by a median Overall Survival (OS) of 12-20 months.
Several STS subtypes, however, have been shown to express PD-L1, and
immune checkpoint inhibitors (ICI) have demonstrated principle anti-tu-
mor activity in pretreated STS.
Methods: MEDISARC is a multi-center phase II trial that is enrolling
adult treatment-naïve pts with histologically conrmed STS of intermedi-
ate or high grade (FNCLCC) not amenable to surgery with curative intent
and ECOG status 0-2. Chemosensitive histologic STS are eligible. 100 pts
will be randomized 1:1, stratied by ECOG status. Pts in the experimental
arm are treated with xed doses of durvalumab (Q4W) and tremelimum-
ab (Q4W for 3 cycles, then Q12W) until Progressive Disease (PD) or for
a maximum of 12 months. Doxorubicin treatment in the standard arm is
(Q3W) limited to 6 cycles. OS is the primary endpoint. Secondary end-
points include 2-year OS rate, PFS, ORR, safety, tolerability, and health-re-
lated quality of life (EORTC QLQ-C30). e accompanying translational
research aims to identify prognostic and predictive biomarkers.
Results: 14 centers in Germany are taking part. Enrollment of pts started
in April 2018 and is ongoing.
Conclusions: Our ongoing clinical trial tests the activity and safety of
ICI combination therapy in the 1st line setting. We hypothesize that the
dual checkpoint blockade with Durvalumab (PD-L1) and Tremelimumab
(CTLA-4) improves overall survival in STS when compared to the stan-
dard of care doxorubicin.
EudraCT No: 2016-004750-15, ClinicalTrials.gov ID: NCT03317457
Reference:
1. J Clin Oncol 37, 2019 (suppl; abstr TPS11075), Abstract & Poster. © 2019
American Society of Clinical Oncology, Inc. Reused with permission. is
abstract was accepted and previously presented at the 2019 ASCO Annual
Meeting. All rights reserved.
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Index
2018
782
Impact of Sarcopenia (SMI(+)) In Patients (PTS) with
Advanced or Metastatic Soft Tissue Sarcoma (A/MSTS) during
Multimodal Therapy (MT) as Risk Parameter
Bennet Hensen 1; Dennis Strassmann 2; Viktor Grünwald 3;
Katharina Stange 2; Hendrik Eggers 2; Florian Länger 4; Martin Panzica 5;
Patrick Zardo 6; Hans Christiansen 7; Frank K. Wacker 1; Arnold Ganser 2;
Philipp Ivanyi 2
1Medizinische Hochschule Hannover, Institut für Diagnostische und
Interventionelle Radiologie, Hannover, Deutschland
2MHH, Klinik für Hämatologie, Hämostaseologie, Onkologie und
Stammzelltransplantation, Hannover, Deutschland
3Universitätsklinikum Essen, Essen, Deutschland
4Medizinische Hochschule Hannover, Institut für Pathologie, Hannover,
Deutschland
5Medizinische Hochschule Hannover (MHH), Klinik für Unfallchirurgie,
Hannover, Deutschland
6Medizinische Hochschule Hannover (MHH), Klinik für Herz-, Thorax-,
Transplantations- und Gefäßchirurgie, Hannover, Deutschland
7Medizinische Hochschule Hannover (MHH), Klinik für Strahlentherapie und
Spezielle Onkologie, Hannover, Deutschland
Purpose: Objective parameters in a/mSTS identifying ideal pts for MT are
hardly dened. erefore, impact of sacropenia (SMI+) in MT treated a/
mSTS pts were analyzed retrospectively.
Methods: 89/181 identied pts from 12/98-6/16 with a/mSTS were evalu-
able for analysis (CTs: -14 days before chemotherapy (CTx) onset). Within
perinterventional CTs, lumbar skeletal muscle index (SMI) was measured
with MeVisLab 2.7 by manual segmentation. Optimal tting method de-
ned SMI cut-o (SMI(+) in males (<44) and females (<38). Clinical or
radiological judgment dened progression (cPFS). Descriptive statistics,
Kaplan-Meier-analysis and Cox-regression were administered.
Results: Overall, at onset of CTx 28/89 pts (31%) suered from SMI(+),
and this was associated with overall less aggressive treatments, lower
numbers of medical treatments, less frequently performed surgery, while
radiotherapy was administered more oen. SMI(+) was associated with
less benet from rst line medical treatment compared to SMI(-) (clin-
ical benet rate: 25% vs. 49.2%, p=.032, PFS: 1 (95%-CI: .35-1.65) vs. 2
(95%CI: .67-3.32) months, p=.006). OS was shortened in SMI(+) com-
pared to SMI(-) pts (4 (95%CI:2-6) vs. 16 (95%CI:8.8-23.2) months,
p=.002). SMI(+) tends to be associated with reduced PFS (HR: 1.7 (95%CI:
0.9-2.8), p=.067) and was independently associated with reduced OS (HR:
2.53 (95%CI: 1.5-4.2), p<.001).
Conclusions: a/mSTS pts with sarcopenia tend to receive less aggressive
therapies. A trend of inferior PFS and an independent risk for reduced
OS was identied in SMI(+) pts. However, this analysis is limited due to
its sample size. None the less, SMI(+) might reect an attractive tool for
treatment intensity modulation in a/mSTS patients, avoiding overtreat-
ment in this cohort with dismal prognosis.
Skin Cancer, including Melanoma
Poster
29
Surgical Treatment of Facial Basal Cell Carcinoma (FBCC). 30
Years of Retrospective and Prospective Studies
Lutz Tischendorf
Praxis MKG Chirurgie, Halle (Saale), Deutschland
Purpose: FBCC are mainly treated surgically. ere are dierences con-
cerning details of the treatment, which is why own studies are summa-
rized as decision-making aid.
Methods: Long-term analyses by means of control of the course of the
disease and reevaluation of the histology. Target criterion: Recurrence
(Kaplan-Meier estimate maximum 25 years).
Retrospective analysis (649 in-patient cases 1948 -1982): Excision with
distance 5 mm. R1- status evaluated only in 1987. Trend to primary defect
closure.
Prospective analysis (832 out-patient cases 1993 – 2007): Excision
with distance 4 mm. Lateral and basal R1-status evaluated in a day. Pri-
mary defect closure.
Analysis of detailed questions (n> 2000)
Results: Controls show excellent oncological and esthetic results.
Recurrence probability for 10 years is determined by R1 and pretreatment
status:
Untreated retrospective cases (n=445) R0: 1.8% R1: 48% (rate R1: 9%)
Untreated prospective cases (n=754) R0: 2% (rate R1: 3%)
Recurrences retrospective cases (n=248) R0 26% R1: 71% (rate R1: 28%)
Recurrences prospective cases (n= 83) R0: 2% (rate R1: 19%)
Detailed questions:
R1 status does not aect survival. Death as result of the tumor is rare
(<0.3%). Secondary tumors occur at a rate of 30% of the patients, with
5% dying. FBCC shortens life expectancy by 5 years compared to normal
population. Unfavorable are locally extended and multicentric FBCCs.
Most FBCCs can be operated on an out-patient basis. Walking disabil-
ities, compliance and blood coagulation disorders can constitute a limita-
tion. Age does not aect prognosis. Complications are rare (4%).
In uncertain basal R1 resections a second-look operation is better than
radiotherapy.
Conclusions: FBCC can be surgically eective treated and oen on an
out-patient basis. Prognostically decisive is the R1-status. Sucient safety
distance as well as lateral and basal marginal cut controls leads to high
oncological safety.
55
Multiplex Tissue Analysis of the Tumor Microenvironment and
Crucial Factors in Melanoma Pathogenesis
Christian Ostalecki 1; Jung-Hyun Lee 2; Stephan Schierer 1; Lena
Collenburg 1; Gerold Schuler 1; Andreas Baur 1
1Universitätsklinikum Erlangen, Hautklinik, Erlangen, Deutschland
2University of Chicago, Department of Microbiology, Chicago, United States
Purpose: Investigation of the early events of melanocyte transformation
by systematically analyzing human tissue sections by the MELC technol-
ogy.
Methods: e study was made possible by applying the so-called MELC
technology. With this technique, it is possible to visualize up to 100 and
more individual antigens on one tissue section, while preserving the
sub-cellular structure and organization of the sample.
Results: Our analysis reveals that ADAM10 activation is a key step in
the transition from dysplastic nevi to a malignant cell. We detailed this
mechanism and found that a change of the subcellular localization of the
endopeptidase SPPL3 is the crucial event towards malignant transforma-
tion, because this event co-localized ADAM10 with its upstream activator
SPPL3. To get this insight, we systematically analyzed human skin tissue
sections from healthy skin to invasive melanoma. Analyzing the protein
prole in the keratinocyte microenvironment surrounding melanoma
cells was instrumental in our study as it reected the individual steps
of the transformation process. e molecular mechanism we uncover is
plausible as we demonstrate how SPPL3-mediated activation of ADAM10
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is functionally embedded in-between downstream eects of BRAFV600E
and the inactivation of PTEN, two established key players in melanocyte
transformation.
Conclusions: e results of our approach are remarkable not only for the
introduction of novel eectors, but for the involvement of rarely described
factors in the transformation process, including protein levels, their sub-
cellular distribution and the early keratinocyte microenvironment. In
summary, we demonstrate that systematic tissue antigen screening in
combination with molecular analysis provides truly novel insight into
melanoma development.
74
Prevention of Skin Cancer among Outdoor Workers
Anette Dr. Wahl-Wachendorf
AMD der BG BAU GmbH, Berlin, Deutschland
Purpose: Recognized as an occupational disease are squamous cell carci-
noma and multiple actinic keratosis. Skin cancer is currently the second
most common occupational disease.
Preventive measures have a high impact. In the AMD der BG BAU, we
have conducted precautionary and advisory work on preventive measures
and early detection of skin cancer since 2015.
In Germany, about 3 million outdoor workers are employed, mostly in
the construction industry and agriculture sector.
Experience with preventive measures, such as head protection, sun-
screen and its acceptance, as well as experience with training in training
centers, using modem technologies will be presented.
e AMD der BG BAU consultations and preventive medical
examinations for outdoor workers in the construction industry. In
particular, carcinoma in situ, actinic keratosis and suspicious squamous
cell lesions are identied and subsequent dermatological evaluation are
recommended.
e current concept for the prevention of skin cancer should be put
up for discussion.
Methods: Please copy and paste the corresponding text here.
Results: Please copy and paste the corresponding text here.
Conclusions: Please copy and paste the corresponding text here.
320
Nico: Real World Evidence in Advanced Melanoma; A
National Prospective Non-Interventional Study of Nivolumab
Monotherapy or in Combination with Ipilimumab in Patients
with Advanced Melanoma and in Patients with Adjuvant
Nivolumab Therapy
Dirk Schadendorf 1; Thomas Eigentler 2; Peter Mohr 3; Michael
Weichenthal 4; Daniela Göppner 5; Sebastian Haferkamp 6; Martin Herber 7;
Friedegund Meier 8; Frank Meiß 9; Claudia Pföhler 10; Stefan W. Schneider 11;
Patrick Terheyden 12; Jens Ulrich 13; Jochen Utikal 14; Carsten Weishaupt 15;
Ralf Gutzmer 16
1Department of Dermatology, Venerology and Allergology, University-Hospital
Essen, University of Duisburg-Essen, Essen
2Center for Dermatooncology, Department of Dermatology, Eberhard-Karls-
University of Tuebingen, Tuebingen
3Elbe Clinic Buxtehude, Buxtehude
4Department of Dermatology , University Hospital Schleswig-Holstein, Kiel
5Clinic for Dermatology and Allergology, Justus-Liebig-University, Gießen
6Department of Dermatology, University of Regensburg, Regensburg
7Bristol-Myers-Squibb GmbH & Co. KGaA, München
8Department of Dermatology, Dresden University Hospital and Medical Faculty
Carl Gustav Carus, Technical University of Dresden, Dresden
9Department of Dermatology, Medical Center - Faculty of Medicine, University
of Freiburg, Freiburg
10Department of Dermatology, Saarland University Hospital, Homburg/Saar
11Department of Dermatology and Venerology, University Hospital Hamburg-
Eppendorf, Hamburg
12Department of Dermatology, University of Luebeck, Lübeck
13Department of Dermatology, Harzklinikum Dorothea Christiane Erxleben,
Quedlinburg
14Department of Dermatology, Venereology and Allergology, University Medical
Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim
15Departments of Medicine A - Haematology, Haemostaseology, Oncology, and
Pneumology, University Hospital Muenster, Muenster
16Division of Immunodermatology and Allergy Research, Department of
Dermatology and Allergy, Hannover Medical School, Hannover
Purpose: Nivolumab alone (nivo) and the combination of nivolumab
and ipilimumab (nivo+ipi) for rst and subsequent lines of therapy have
become standard treatment options for advanced melanoma. Most cur-
rently available data are from randomized clinical trials with predened
inclusion/exclusion criteria. erefore, real-world studies are needed to
evaluate the eectiveness and tolerability of nivo and nivo+ipi in a broader
patient population.
Methods: NICO (NCT02990611) is an ongoing, non-interventional study
in Germany associated to ADOREG.
Overall, 950 patients with advanced melanoma, who start therapy with
nivo+ipi or nivo (cohort 1+2, n=750) or with nivo adjuvant therapy (co-
hort 3, n=200) according to marketing authorization in Germany, will be
enrolled. Patients are followed for up to 5 years aer initiation of ther-
apy. e primary objectives are overall survival (OS) in patients receiv-
ing nivo+ipi and relapse-free survival in patients starting nivo adjuvant
therapy. Secondary objectives include OS in patients treated with nivo,
progression free survival, adverse event management and patient-report-
ed outcomes.
Results: Baseline data of 359 nivo+ipi and 205 nivo patients are currently
available, at the next data cut 30.09.2019, interim data of approx. 610 pa-
tients of cohorts 1+2 will describe baseline characteristics and outcome
of patients with a minimum follow-up of 6 months. e data further
provides demographic and disease characteristics of approx. 130 patients
of cohort 3 and comprises safety management of more than 600 treat-
ment-related adverse events documented so far.
Conclusion: We provide the rst eectiveness data of the NICO obser-
vational study in patients treated with nivo or nivo+ipi in routine care
in Germany. Furthermore, information about baseline characteristics in
adjuvant patients and the management of immune related adverse events
in clinical practice is shown. Taken together, these data give valuable in-
sight in the current treatment landscape and outcome in patients with
advanced melanoma.
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541
Topography-, Age- and Sex-Specic Incidence and Relative
Survival of Cutaneous Squamous Cell Carcinoma in North
Rhine-Westphalia, Germany, 2007-2015
Andreas Stang 1, 2; Ina Wellmann 3; Hiltraud Kajueter 3; Jürgen C. Becker 4;
Adele Green 5; Karl Heinz Jöckel 1; Laura Khil 3
1Institut für Medizinische Informatik, Biometrie und Epidemiologie,
Universitätsklinikum Essen, Essen, Deutschland
2Department of Epidemiology, School of Public Health, Boston University,
Boston, United States
3Krebsregister Nordrhein-Westfalen, Bochum, Deutschland
4Department Translational Skin Cancer Research (TSCR), University Hospital of
Essen, Essen, Deutschland
5QIMR Berghofer Medical Research Institute, Herston, Australien
Purpose: Nonmelanotic skin cancer is frequently not registered by popu-
lation-based cancer registries. e cancer registry of North Rhine-West-
phalia (LKR-NRW) registers these tumors. e aim of this study is to
assess how the incidence and survival of cutaneous squamous cell carci-
noma (SCC) depends on age, sex, and topography.
Methods: With data of the LKR-NRW of the years 2007-2015, we esti-
mated incidence rates (age-specic and age-standardized, European stan-
dard) and age-standardized relative 5-year survival of SCC (genital skin
and remaining skin) by sex and topography.
Results: Overall, 83,650 cases were registered with 8.7% at the skin of the
genitalia (men: 3.0%, women: 16.2%). e SCC incidence of the genital
skin and the remaining skin has increased over time. Age-specic inci-
dence rates of SCC at the genital skin were higher in women than men in
each age group. At the remaining skin, men had higher SCC incidences at
each subsite than women, with the exception of skin of the legs. Age-spe-
cic incidence patterns show two distinct patterns dependent on the lo-
calization. Survival was considerably lower for SCC at the genital skin
(men: 71%, women: 75%) than at the remaining skin (men: 93%, women:
97%). Survival is especially low for SCC at the scrotal skin (67%) and labia
majora (62%).
Conclusions: e increase of the incidence of SCC may be explained by
the introduction of the skin cancer screening program and to some in-
crease in the completeness of registration. When comparing age-specic
incidences between men and women, the age-specic patterns depend on
the localization of the tumors. SCC of the genital skin show a considerably
lower 5-year survival than SCC of the remaining skin.
Disclosure Statement: See extra le.
654
Endocrine Side-Eects inImmune Checkpoint Inhibitor
Combinational (Nivolumab+Ipilimumab) Therapy for
Melanoma Associate with Increased Survival
Caroline Weller 1; Klaus Badenhoop 2; Ümniye Balaban 3;
Roland Kaufmann 1; Markus Meissner 1
1Klinik für Dermatologie, Venerologie und Allergologie, Goethe Universität
Frankfurt, Frankfurt, Deutschland
2Medizinische Klinik 1; Abteilung für Endokrinologie, Goethe Universität
Frankfurt, Frankfurt, Deutschland
3Institut für Biostatistik und mathematische Modellierung , Goethe Universität
Frankfurt, Frankfurt, Deutschland
Purpose: Although previous studies suggest that the endocrine side ef-
fects of immune-checkpoint inhibitor (ICI) combinational therapy with
ipilimumab and nivolumab are underestimated, there is a lack of focused
evaluations and consistent denitions in the clinical setting. e possible
inuence of endocrine side eects on overall survival are up to now not
clearly addressed and should be evaluated in this study.
Methods: In this monocentric retrospective study, patients with ICI com-
binational therapy (Nivolumab + Ipilimumab) in metastatic malignant
melanoma were included. Patients with start of therapy from March 2016
to September 2017 and a follow up period until July 2019 were included.
e incidence, course and therapy of thyroiditis, hyperthyroidism,
hypophysitis including Addisonian crisis and the eects on overall sur-
vival were analyzed.
Results: 44 patients could be included in this study. ere were 27 (61.4%)
dierent endocrine side eects in 22 (50%) patients. Mild to asymptomat-
ic thyroiditis (27.3%) with transient thyrotoxicosis was most frequent aer
a median of 20.5 days (± 11.04) followed by irreversible hypothyroidism
aer a median of 52 days (± 21.12). Hypophysitis was observed in 11.4%
of the treated patients aer a median of 41 days (± 27.58) with resulting
treatment pauses and irreversible adrenocortical insuciency. Endocrine
side eects signicantly correlated with improved overall survival (p =
0.02). e median overall survival was 36 month in the side eect group
versus 7 month in patients without endocrine adverse events.
Conclusions: Endocrine adverse events during ICI combinational thera-
py are more common in the clinical setting than previously thought. Due
to the signicantly improved survival, an increased anti-tumoral activity
can be assumed when endocrine side eects occur.
Disclosure Statement: CW, KB, RK: no conict of interest; MM: Advisory and
speaker function for BMS, MSD, Merck.
709
With Three-Dimensional Histology, the Area of the Studied
Resection Margins of Excidates is up to 5,000 Times Higher
than with Conventional Histology
Irina Belova
Charité - Universitätsmedizin Berlin, Chirurgische Klinik (CVK), Berlin,
Deutschland
Purpose: In a conventional histology (CH) using parallel cuts, the areas
between the slices remain unrepresented in the histological slides, which
can lead to incomplete removal of the tumor along the resection margin
(RM) and worsen the treatment results. For guaranteed detection of tu-
mor inltrates in the RM, the excidate should be prepared by 3D histology
(3D H): separating the thin vertical lateral margin strip (marginal section
(S)), then horizontal – a thin layer of the lower side (basic S) and nally – a
cross section of the remaining middle part (middle S). Marginal and basic
S are to be examined for the presence of tumor inltrates, and the mor-
phological type of the tumor is determined by the middle S. We compared
the eciency of 3D H and CH in skin cancer using a mathematical model.
Methods: 18 variants of sizes of excidates in the form of a circular cylin-
der were examined: 1, 2, 3, 5, 7, 10 cm in diameter and 0.5, 1 and 1.5 cm
in height. It was assumed that for CH, excidates are prepared as follows:
with a diameter ≤ 2 cm – in parallel S completely, starting from the center
(middle S), and from it – to the margins of the excidate, and with a diam-
eter > 2 cm, three S were made in the center and one on each sides of the
excidate. e thickness of the S both in CH and in 3D H was taken to be
2 mm. Aer paranization, histological ne slices, 5 microns thick, were
made and examined under a microscope: in the CH – from the center of
each S, and in 3D H – from the outer margin of the S. e percentages of
the studied area of RM in 3D H and CH were calculated and compared,
the percentage of the area of useful examination (to determine the tumor
type and to detect tumor inltrates along the RM) in the total studied area
was determined.
Results: CH provides a check of the RM by only 0.02-0.2%, and 3D H – by
85-100%. In CH with 5 S – 70-75%, and with 9 S – 87% of working time
and expendable material is wasted.
Conclusions: CH does not guarantee the detection of tumor inltrates
in the RM and does not protect the patient from recurrence aer surgical
removal of the tumor. It is more reasonable to use 3D H for the evaluation
of the excidate with skin cancer.
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816
Treatment Reality of Patients with BRAF-Mutant Advanced/
Metastatic Melanoma in Germany, Austria and Switzerland in
the Era of Choice
Sebastian Haferkamp 1; Ingrid Wolf 2; Mareike Alter 3; Dirk Debus 4;
Bastian Schilling 5; Robert Hunger 6; Patrick Terheyden 7;
Camille Lea Gerard 8; Deborah Zihler 9; Andreas Pinter 10; Jochen Utikal 11;
M. Sachse 12; Thomas Haalck 13; Ralph Zachariah 14; Johanna Mangana 15
1Klinik und Poliklinik für Dermatologie, Universitaetsklinikum Regensburg,
Regensburg, Deutschland
2Dermatologie und Venerologie, Universitaetsklinikum Graz, Graz, Österreich
3Klinik für Dermatologie und Venerologie, Universitätsklinikum Magdeburg,
Magdeburg, Deutschland
4Hauttumorzentrum Nürnberg, Paracelsus Universität, Nürnberg, Deutschland
5Hautklinik, Universitätsklinikum Würzburg, Würzburg, Deutschland
6Abteilung Dermatologie, Universitätsspital Bern, Bern, Schweiz
7Hautklinik, Universitaetsklinikum Schleswig-Holstein
8Oncology Department, Université de Lausanne, Lausanne, Schweiz
9Abteilung für Onkologie, Hämatologie und Transfusionsmedizin, Kantonsspital
Aarau AG , Aarau, Schweiz
10Klinik für Dermatologie Venerologie und Allergologie, Universitätsklinikum
Frankfurt, Frankfurt, Deutschland
11Deutsches Krebsforschungszentrum (DKFZ) , Universität Heidelberg,
Heidelberg, Deutschland
12Klinik für Dermatologie, Allergologie und Phlebologie, Klinikum Bremerhaven
Reinkenheide gGmbH, Bremerhaven, Deutschland
13Ambulanzzentrum des UKE GmbH, Universitätsklinikum Hamburg-Eppendorf,
Hamburg, Deutschland
14Medizinische Onkologie und Hämatologie, Kantonsspital Winterthur,
Winterthur, Schweiz
15Dermatologische Klinik, Universitätsspital Zürich, Zürich, Schweiz
Purpose: Due to the rapid development of the treatment landscape,
multiple options are available for the treatment of patients (pts) with
BRAF-mutant advanced/metastatic melanoma. Targeted therapies (TT)
of BRAF and MEK inhibitor combinations or checkpoint inhibitors (IO)
in monotherapy or in combination are used. e present analysis shows
the current treatment choices and their reasons in daily routine treatment
in Germany, Austria and Switzerland.
Methods: Retrospective and anonymous documentation of the rst- to
third-line treatments outside of clinical trials (treatment start between
January 2016 and September 2018) in pts with advanced/metastatic
BRAFV600E/K-mutant melanoma and the reasons for treatment choice.
Results: Data of 140 pts treated with 242 treatment lines at 15 clinics were
analyzed (52% male; median age 59 years, ECOG PS 0 or 1: 75.7%; ele-
vated LDH: 34.3%; stage IV M1c: 25.0%; M1d: 22.1%). 74 pts entered the
second and 28 pts the third line treatment. e choice between TT and IO
was well-balanced (1st: TT 50.7%; IO 49.3%; 2nd: TT 50.0%; IO: 45.9%).
In general, the treatment type was switched between the treatment lines.
e main reason for choosing a treatment type were remission pressure
for TT and physicians preference for IO. For TT, dabrafenib + trametinib
was predominantly administered (70.0%); vemurafenib + cobimetinib
was used in 26.0% of the pts. For IO, more pts received monotherapy reg-
imens (56.3%) than combination treatment (43.8%). e main reasons for
choosing specic drugs were their toxicity proles (TT) and physicians
preference (IO). Main reasons for treatment discontinuation were pro-
gression (TT 45%; IO 45%) and toxicities (TT 15.0%, mostly dermatolog-
ical; IO 17.9%, mostly gastrointestinal (nearly all in IO combinations)).
Conclusions: In the treatment of patients with BRAF-mutant advanced/
metastatic melanoma, modern substances were used with an equal distri-
bution between TT and IO. e reasons for choosing between TT and IO,
or substances within the groups, were dierent.
Disclosure Statement: Financing by Pierre Fabre Pharma.
823
Single Center Experience: Use of Talimogene Laherparepvec
(TVEC) in the Elderly: A (COST)-Eective Therapy-Option with
Low Side-Eects ?
Johannes Kleemann; Manuel Jäger; E. Valesky; Roland Kaufmann;
Markus Meissner
Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum
Frankfurt, Frankfurt am Main, Deutschland
Purpose: Talimogene laherprapevec (T-VEC), a genetically modied her-
pes simplex virus (HSV-1), has been approved for the intralesional ther-
apy of locally advanced malignant melanoma (AJCC IIIB- IVM1a) since
2016 in Germany. In the randomized controlled Phase III trial (OPTiM),
T-VEC achieved in the above cohort a response rate (ORR) of 46.0% and
a durable response rate of 28.8%. Adverse event grade 3 or higher were
rare. To date, little data is available on the use of T-VEC outside of clinical
trials, particularly with regard to the treatment needs of elderly patients.
Methods: In the present retrospective evaluation we examined the data of
11 elderly patients(minimum age of 65 years at the start of treatment) suf-
fering from malignant melanoma , who were treated with T-VEC outside
of clinical trials at the University Hospital Frankfurt from August 2016
to May 2019. erapy response was measured by overall response rate
(ORR) and sustained tumor response rate (DRR). Patient specic data,
side eects and therapy costs were collected and evaluated.
Results: 82% (n=9) of the patients were in AJCC stage III at the start of
therapy, 18% (n=2) in IVM1a. e median age was 83 years. 18% (n=2)
of the patients under therapy with T-VEC achieved a complete response,
55% (n=6) had a partial remission, 9% (n=1) achieved a stable disease and
18% (n=2) showed progressive disease. us, the tumor control rate was
82% (n=9). Treatment related irreversible and serious side eects (≥ grade
3) were not observed. One patient died of a non-associated myocardial
infarction during the observation period. e mean therapy costs in the
investigated population were in the same range as the minimum annual
therapy costs of T-VEC according to pharmacy retail prices.
Conclusions: In this special cohort of elderly patients, the high tumor
control rate of 82% shows a good ecacy of T-VEC in the therapy of ma-
lignant melanoma under real-life conditions. With the regard to the short
average duration of treatment and the low side eect rate, T-VEC oers a
good therapy alternative for aged patients
856
Validation of the 8th Edition TNM Classication For Stage III
Melanoma Patients in a Single German Referral Center
Nina Stöckle 1; Axel Hauschild 1; Katharina Kähler 1; Michael Weichental 1
1Universität Kiel, Klinik für Dermatologie, Kiel, Deutschland
Purpose: In the 8th edition of the AJCC and UICC TNM classica-
tion rules for melanoma with locoregional spread (stage III) have been
changed substantially. As a result, the estimated 5-year survival rates for
e.g. stage IIIA have improved dramatically, making stage IIIA more favor-
able than stage IIB and IIC. Concerns have been raised as to the validity of
the underlying outcome database, still some retrospective re-evaluations
suer from potential selection bias during follow-up.
Methods: We attempted to evaluate 5-year survival follow-up for stage
III melanoma patients diagnosed between with a loss-to-follow-up rate
below 10% and with a primary focus on prospectively followed primary
diagnoses. We evaluated releapse-free survival (RFS) and overall survival
(OS) and calculated 5-year rates using Kaplan-Meier product limit
estimates.
Results: We present follow-up data on 277 patients with 7th edition stage
III melanoma primarily diagnosed between January 1 2003 and Decem-
ber 31 2013. e estimated melanoma specic 5-year survival rates were
87.8%, 78.7%, 57.4%, and 25.0% in stages IIIA (n=49), IIIB (n=74), IIIC
(n=143), and IIID (n=8), respectively.
Conclusions: e usability of the new TNM classication for stage III
melanoma could be conrmed. Survival rates where higher as compared
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2018
Index
2018
to the corresponding 7th edition rates, but somewhat lower as published by
the AJCC melanoma international database.
Reference:
1. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-ba-
sed changes in the American Joint Committee on Cancer eighth edition cancer
staging manual. CA Cancer J Clin 2017;67:472-92. on cancer eighth edition
cancer staging manual. CA. Cancer J. Clin. 2017;67:472-492
Disclosure Statement: none to disclose.
Supportive Care
Vorträge
743
Institutional Strategies for Addressing Complementary or
Alternative Medicine (CAM). A Qualitative Study with Health
Professionals in (Pediatric) Oncology
Ulrike Handke 1; Pia Klatt 2; Jan Schildmann 3; Christin Kohrs 2;
Barbara Stein 2; Markus Horneber 1; Daniela Reis 4; Alfred Längler 4
1Universitätsklinik für Innere Medizin 5 – Schwerpunkt Onkologie/Hämatologie,
Paracelsus Medizinische Privatuniversität, Klinikum Nürnberg, Nürnberg,
Deutschland
2Universitätsklinik für Psychosomatische Medizin und Psychotherapie,
Paracelsus Medizinische Privatuniversität, Klinikum Nürnberg, Nürnberg,
Deutschland
3Institut für Geschichte und Ethik der Medizin , Martin-Luther-Universität Halle-
Wittenberg, Halle (Saale), Deutschland
4Universität Witten/Herdecke, Fakultät für Gesundheit, Professur für integrative
Kinder- und Jugendmedizin, Gemeinschaftskrankenhaus Herdecke, Abteilung
für Kinder- und Jugendmedizin, Herdecke, Deutschland
Purpose: is paper explores attitudes and experiences of health profes-
sionals in (pediatric) cancer care whether - and if so, how CAM consulta-
tion and/or treatment should be integrated into clinical care.
Methods: Qualitative semi-structured in-depth interviews with experts
in (pediatric) oncology in Germany. Sampling started from a convenience
sample with subsequent elements of snowball sampling. All interviews
were audiotaped and transcribed ad verbatim. Qualitative analysis of
data was conducted according to principles of content analysis by two re-
searchers independently.
Results: Interviews were conducted with 15 pediatric oncologists, 13
physicians with clinical experience in the care of adult cancer patients,
2 nurses, 2 psychologists and 1 dietician. Interviewees understanding
of CAM varied considerably. ere was agreement among interviewees
regarding a perceived need for institutional services on information and
possible CAM treatment oers. Reported examples of individual activities
to inform about or provide CAM measures were usually initiated by sin-
gle professionals with strong interest in CAM but not embedded into an
overall institutional strategy. Lack of evidence was not a general reason for
refusal, in fact integrating CAM measures was viewed by some as a chance
to create an evidence-base. Structural challenges encompassed nancial
resources, time and rooms allocated to the provision of such services. e
acceptance by health professionals was quoted as another relevant factor
furthering or hindering the institutional implementation of CAM (infor-
mation) services in cancer care.
Conclusions: e interviewed experts in principle agree on the need
for establishing CAM related services on an institutional level. However,
there were dierences regarding their understanding of CAM and the ele-
ments of CAM related services.
Disclosure Statement: is work is part of the collaborative research project
“Kompetenznetz Komplementärmedizin in der Onkologie – KOKON”, funded by
Stiung Deutsche Krebshilfe, Bonn, Germany (Project No. 70112458)
Poster
28
Feasibility of Yoga Intervention in Curative and Palliative
Cancer Patients with Fatigue
Teresa Zetzl; Agnes Renner
Interdisziplinäres Zentrum Palliativmedizin, Universitätsklinikum Würzburg,
Würzburg, Deutschland
Purpose: Yoga interventions achieve growing attention in cancer care to
reduce side eects of the treatment 1. e purpose of this pilot study was
to test the feasibility of an 8-week yoga-therapy for palliative and curative
oncological patients who suer strongly from fatigue. We want to inves-
tigate the eectiveness and any necessary changes to the program or re-
cruitment.
Methods: e eligible participants (fatigue intensity ≥4, impairment ≥ 5)2
were randomly assigned to either the intervention group (IG) or the con-
trol group (CG). e IG received 8 units of yoga, one hour per week. At
the beginning and aer 9 weeks, fatigue, quality of life (QoL) and depres-
sion were assessed by questionnaire.
Results: Within a recruitment period of 5 months, 25 out of 241 eligi-
ble patients were enrolled for the study (participation rate=10.3%). e
participants (12 IG, 13 CG), mean age 61.8 years (STD 13.15), were 76%
women, 20% under palliative treatment and predominantly aected by
breast cancer (56%). 66% of participants in IG attended more than 50%
of yoga classes. 6 participants (3 IG/3 CG) discontinued the study due
to overlapping appointments (33%), poor general condition (33%) or no
reasons given (33%). e satisfaction regarding yoga class (5.9/6), selec-
tion of yoga poses (5.6/6) and instruction by the yoga therapists (5.8/6)
was very high.
In an explorative peer-protocol analysis with participants who attend-
ed more than 50% of the yoga classes signicant dierences in depres-
sion score (time x group interaction) were reported (p=.007, d=1.63). No
signicant interactions were found in physical, emotional and cognitive
fatigue and QoL.
Conclusions: ese initial results suggest that yoga is well accepted and
should be further explored with a larger sample size. Due to the low par-
ticipation rate the inclusion and exclusion criteria must be discussed. Fur-
ther research should be done into the reasons for non-participation in
order to reduce it.
References:
1. Buart et al., 2012
2. Fischer, 2013
Disclosure Statement: TZ and AR report grants from Deutsche Krebshilfe, during
conduct of study
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2018
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2018
124
Prio-Practical and Patient-Oriented Recipe Development for
Oncology Patients
Barbara Scheerer 1; Daniel Buchholz 2; Heike Sanchez 3; Jana Schmunz 4;
Walburga Träger 5; Lars Selig 6; Volker Heinemann 1; Nicole Erickson 1
1 Ludwig Maximilian‘s University, Krebszentrum – CCC MünchenLMU –
Comprehensive Cancer Center, München, Deutschland
2Universitätsmedizin der Johannes Gutenberg-Universität Mainz , Staatlich
anerkannte Schule für Diätassisten
3Universtitätsklinikum Ulm, Akademie für Gesundheitsberufe | Schule für
Diätassistenz, Ulm-Wiblingen, Deutschland
4Charité Gesundheitsakademie , Ausbildungsbereich Diätassistenz, Berlin,
Deutschland
5St. Franziskus – Schule für Gesundheitsberufe , Schule für Diätassistenten,
Münster, Deutschland
6Universitätsklinikum Leipzig, Ernährungsteam/Ernährungsambulanz, Leipzig
Purpose: While nutrition recommendations play an integral role in the
maintenance of nutrition status, it is important to dene barriers und fa-
cilitators to the implementation of nutrition recommendations and pro-
vide practical patient-oriented, scientically based solutions.
Methods: In this mixed methods study, the Patient Generated Subjective
Global Assessment provided validated quantitative information pertain-
ing to nutrition-related symptom burden (NRSB), and nutrition status.
Qualitative methods provided criteria for development of recipes targeted
at NRSB and the nal questionnaire assessing barriers und facilitators to
the implementation of nutrition recommendations, which will be ana-
lyzed quantitatively via SPSS v.25.
Results: Following the criteria elicited from structured interviews with
patients (n=8) and professionals (n=10), 52 recipes aimed at easing the
NRSB were developed, and pre-tested for taste, texture, appearance, and
ease of preparation in the test kitchens by dietitians and dietetic students
spread over 7 locations in Germany. Selected recipes are further being
quantitatively assessed for acceptance and utility. Recruitment is ongoing
(so far n=45) for the questionnaires which will be analyzed quantitatively
in Autumn 2019.
Conclusions: is study will contribute to a more practicable, patient-
oriented approach to managing the NRSB and provide suggestions for
tailoring information aimed at malnutrition prevention. Results along
with exemplary recipes will be presented at the Congress. Free access to
the recipes via internet will be provided.
References:
1. Beehler et al. Mil Med. 179, 9:998, 2014.
2. Conradie et al. S Afr J Clin Nutr 2009;22(4):177-184
Disclosure Statement: DKG provided nancial support.
134
Education about Complementary Medicine: Evaluation of a
Concept for Leaders of Cancer Self-Help Groups
Martina Jablotschkin 1; Hans Helge Bartsch 2; Markus Horneber 3;
Joachim Weis 1
1Comprehensive Cancer Center - Department of Cancer Self-help Research,
University Clinic Center Freiburg, Freiburg, Deutschland
2University Clinic Center Freiburg, UKF Reha gGmbH - Department of
Oncological Rehabilitation, Medical Center, Freiburg, Deutschland
3Paracelsus Medical University, Klinikum Nuernberg, Department of Internal
Medicine - Divisions of Oncology/Hematology and Pneumology, Nürnberg,
Deutschland
Purpose: Many cancer patients have a need for information about com-
plementary and alternative medicine (CAM). e purpose of the study
(KOKON subproject P7, funded by German Cancer Aid) [1] was to im-
plement and evaluate a CAM educational concept for group leaders of
cancer self-help groups, which was developed in a pilot study in cooper-
ation with health professionals and representatives of cancer patients ad-
vocacy organizations. Its aim was to promote an open exchange of expe-
riences with CAM, to impart reliable information sources and to sensitize
for untrustworthy CAM oers.
Methods: Self-help group leaders were trained in Germany to carry out a
CAM training in their groups. e trainings were evaluated in terms of ac-
ceptance and feasibility by group leaders and members. A follow-up ques-
tionnaire for the group members six months aer the training to prove its
sustainability and potentially changed information seeking behaviors or
attitudes towards CAM will be analyzed at the end of 2019 (T2).
Results: N=49 of N=577 trained group leaders implemented the training
in their groups and felt condent to moderate it using provided mate-
rial. e trained group members (N=419) were satised with selection
and comprehensibility of contents, appreciated the possibility to exchange
CAM experiences and agreed that the training imparts reliable informa-
tion sources, 91% would recommend it.
Conclusions: e preliminary results indicate that this innovative educa-
tional concept could be a good option to inform cancer survivors about
CAM in addition to consultation by experts.
Reference:
1. Witt, C.M., Bartsch, H.H., Güthlin, C. et al. (2017). Kompetenznetz Komple-
mentärmedizin in der Onkologie (KOKON). Ein wissenschalicher Beitrag
zur Verbesserung der Versorgung. Forum 2017. https://doi.org/10.1007/
s12312-017-0311-1
Disclosure Statement: e authors declare that there are no conicts of interest in
terms of the contents of this publication.
157
Whole Body Vibration Exercise Aects Bone Metabolism and
Improves Physical Performance in Patients with Monoclonal
Gammpathy of Undetermined Signicance
Lothar Seefried 1; Bernhard Engelmann 2; Franca Genest 1;
Johanna Strömsdörfer 2; Constantin Lapa 3; Freerk Baumann 4;
Billy Sperlich 5; Franziska Jundt 2
1Orthopädische Klinik König-Ludwig-Haus, Würzburg
2Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg,
Deutschland
3Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg,
Deutschland
4Innere Medizin I, Uniklinik Köln, Deutschland
5Institut für Sportwissenschaft, Universität Würzburg
Purpose: Monoclonal gammopathy of undetermined signicance
(MGUS) is a pre-malignant condition in which abnormal monoclonal
proteins are produced by plasma cells in the bone marrow. Patients with
MGUS have an increased risk for bone fractures potentially due to in-
creased cortical porosity.1 In our clinical pilot study we evaluated the im-
pact of whole body vibration (WBV) exercise on bone turnover, structure
and physical functioning.
Methods: Fieen MGUS patients (62.5 ± 7.8 yr; n=9 female) performed
WBV two times per week for 30 minutes over twelve weeks. Ten patients
continued WBV training for additional twelve weeks. Primary endpoints
were changes in bone density parameters (quantitative computer tomog-
raphy) and bone turnover markers. Measures of functional and activity
testing served as secondary endpoints.
Results: In females (n=9) we observed a signicant increase in bone
structural parameters such as cortical thickness (P=0.016) at the tibia over
24 weeks. In the entire cohort a signicant decrease in the bone biomark-
ers Dickkopf1/DKK1 (P=0.012), Alkaline Phosphatase (P=0.006), was
accompanied by an increase in Sclerostin levels (P=0.015). Highly signif-
icant improvements in physical functioning were measured by the Chair
Rise Test (P=0.001), Timed up and go (P=0.001) and 6-minute Walk Test
(P=0.001) aer 24 weeks. No exercise-related adverse events or skeletal
fractures were observed during the study.
Conclusions: Our study demonstrates that WBV improves bone turnover
parameters and physical functioning, particularly in females with MGUS.
Future studies are needed to show whether WBV has an impact on frac-
ture risk in cancer patients with bone disease.
Reference:
1. Farr JN et al. Blood 2014;123:647.
Disclosure Statement: Nothing to disclose.
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235
Ways to Cancer Counseling Centers: How do People Become
Aware of these Centers?
Melanie Schranz 1; Oliver Bayer 1; Margret Xyländer 2; Britta Büchler 1;
Silke Meier 3; Gudrun Bruns 4; Evelyn Flohr-Schmitt 5; Meike Achenbach 6;
Alexander Wünsch 7; Andreas Ihrig 8; Franziska Petridis 9; Larissa Rudolph 10;
Konstanze Pilgrim 11; Norbert Gelse 12; Thorsten Meyer 2; Susanne Singer 1
1Universitätsmedizin Mainz, IMBEI, Abt. Epidemiologie und
Versorgungsforschung, Mainz, Deutschland
2Universität Bielefeld - Fakultät für Gesundheitswissenschaften, Rehabilitative
Versorgungsforschung, Bielefeld, Deutschland
3Stiftung phönikks, Hamburg, Deutschland
4Tumor-Netzwerk Krebsberatung im Münsterland e.V. , Münster, Deutschland
5Psychosoziale Krebsberatungsstelle Würzburg, Würzburg, Deutschland
6Psychosoziale Krebsberatungsstelle Frankfurt, Frankfurt am Main, Deutschland
7Uniklinik Freiburg, Psychosoziale Krebsberatungsstelle Freiburg, Freiburg,
Deutschland
8Psychosoziale Krebsberatungsstelle Nordbaden, Heidelberg, Deutschland
9Psychosoziale Beratungsstelle der AWO, Karlsruhe, Deutschland
10Universitätsklinikum Leipzig, Abt. Medizinische Psychologie und Medizinische
Soziologie, Leipzig, Deutschland
11Psychosoziale Krebsberatungsstelle Nürnberg, Nürnberg, Deutschland
12Psychosoziale Krebsberatungsstelle Tübingen, Tübingen, Deutschland
Purpose: Cancer counseling centers (in German: Krebsberatungsstellen –
KBS) oer psychological and social (legal) support for patients and their
relatives who are confronted not only with physical but also with psycho-
social burdens as a result of cancer [1]. But how are people made aware
of such places?
Methods: Guideline-based interviews were used in a Germany-wide
qualitative study. 43 patients and relatives were interviewed face-to-face
by trained sta in 10 cancer counseling centers; 30 referring physicians
were interviewed via telephone by the project team. All interviews were
transcribed and evaluated by content analysis [2].
Results: Flyers and information brochures are important sources that
draw the attention of patients and their relatives to KBS. Websites, news-
paper advertisements, and information events were also mentioned. In
addition to public relations work, the personal approach - above all in the
medical care system, but also in the non-clinical and social environment
- was of central importance. Sometimes the referring physicians contact-
ed the KBS directly. Sometimes they even contacted the KBS directly on
behalf of the patients who were clearly struggling. Some physicians ad-
dress KBS routinely, while others only do so when an explicit need arises
(when those seeking advice are (very) burdened and express an increased
psychosocial (legal) counseling need). Disseminated in the medical/clini-
cal care system. As a result, closer cooperation with general practitioners,
social workers, and psychologists should be sought. Informative yers and
brochures can sharpen the focus on KBS and highlight the features that
distinguish it from other outpatient care services. Good public relations
are essential.
References:
1. Giesler JM et al. (2015) Ambulante psychoonkologische Versorgung durch
Krebsberatungsstellen – Leistungsspektrum und Inanspruchnahme durch
Patienten und Angehörige. Psychother Psych Med 65(12): 450-458.
2. Mayring P (2016) Einführung in die Qualitative Sozialforschung, Beltz.
Disclosure Statement: None of the authors have anything to disclose.
241
Spiritual Care in Oncology: Patients’ Perceived Spiritual
Support and Professionals’ Perceived Responsibility to Care
for their Patients´ Spiritual Needs – Data from a Pilot Project
Arndt Büssing 1; Eckhard Frick Sj 2; Jens Büntzel 3
1Professorship Quality of Life, Spirituality and Coping, Institute of Integrative
Medicine, Witten/Herdecke University, Herdecke, Deutschland
2Research Unit Spiritual Care, Clinic for Psychosomatic Medicine and
Psychotherapy, Technical University Munich, München, Deutschland
3Department of Otolaryngology, Palliative Care Unit, Südharz Clinic
Nordhausen, Nordhausen, Deutschland
Purpose: As part of the AG PRIO project on spiritual needs of cancer
patients and spiritual care competences of oncology sta we intended to
analyze the spiritual-religious (S/R) self-categorization of patients and
their health professionals.
Methods: Cross sectional survey in a dened time frame among patients
with cancer from treatment centers in East and West Germany and their
treatment team (i.e. physicians, nurses, psychologists, medical assistants)
with standardized questionnaires.
Results: We analyzed data from 171 patients (62% women; 61±12 years
of age) and from 78 health professions (78% women; 43±11 years of age;
35% physicians, 18% nurses, 47% other; 33% oncology wards, 36% hospi-
tals, 22% university hospital, 8% other). While a majority of sta regarded
themselves as religious and/or spiritual (41% R+S+, 11% R+S-, 9% R-S+,
39% R-S-), most patients stated to be non-religious (16% R+S+, 23% R+S-,
8% R-S+, 53% R-S-). ere were no signicant dierences between East
and West German centers. Among the sta, 33% of S/R and 79% of R-S-
(p<0,001; Chi2) do not feel responsible to care for spiritual issues. Never-
theless, 75% of S/R and 57% of R-S- patients (p=0,056; Chi2) felt supported
in their spiritual needs by the sta.
Conclusions: Health professionals´ and patients´ self-perception of being
spiritual/religious or not diers. is may have an impact on what patients
expect from the sta and how these may respond to their patients´ spiritu-
al needs. Even in widely secularized societies, patients may be aected by
unmet spiritual needs and unresponsive caregivers.
Disclosure Statement: e study was supported by a grant of German Cancer
Society. e authors disclose any conict of interest.
251
PACC: Patient Centered Care
Nicole Erickson 1; Carina Eckhardt 1; Lena Storck 2; Ingrid Ricard 1;
Anita Joos 2; Lian Liu 1; Peter E. Ballmer 2, 3; Friederike Mumm 4;
Christoph Riese 5; Volker Heinemann 1; Theres Fey 1
1 Ludwig Maximilian‘s University, Krebszentrum – CCC MünchenLMU –
Comprehensive Cancer Center, München, Deutschland
2Kantonsspital Winterthur, Department for Medicine, Winterthur
3Zürcher RehaZentrum, Davos-Clavadel, Schweiz
4 Ludwig Maximilian‘s University, Interdisziplinäres Zentrum für Psycho-
Onkologie, München, Deutschland
5CANKADO Service GmbH, Köln, Deutschland
Purpose: Investigation of ecacy of nutrition-related patient reported
outcomes (NR-PRO) and their implications in clinical care.
Methods: Multicenter, multinational trial exploring the acceptability,
perception, and usability of NR-PRO factors assessed using CANKADO’s
E-health platform.
Results: 188 patients undergoing treatment for gastrointestinal tumors in
Germany and Switzerland were asked to complete 79 tablet-based ques-
tions consisting of 2 validated questionnaires related to nutrition status
along with questions pertaining to acceptability. 34 Patients (18%) chose
not participate.152 patients (median age 62 years; range 22-86) were will-
ing to complete the questionnaires. While 84% perceived the tablet-based
questionnaire to be not dicult, older patients tended to nd the tab-
let-based format more unwieldy than younger patients (p=0.052). While
age was similarly distributed between the sexes, men were signicantly
more likely to require help completing the questionnaires than women
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(p=0.035). A high proportion (89%) largely, or completely, agreed that
NR-PROs via tablet should be integrated in routine clinical care.
Conclusions: Routine assessment of NR-PROs via tablet is an acceptable
approach for patients undergoing treatment for gastro-intestinal tumors
and poses a simple and ecient solution for integrating these valuable
assessment parameters into routine clinical care.
References:
1. Gotay C. et al. e prognostic signicance of Patient-Reported Outcomes in
cancer clinical trials. JCO Volume 26 (8) 2008.
2. Erickson N. et al. Tri-country translation, cultural adaptation, and validity
conrmation of the Scored Patient-Generated Subjective Global Assessment.
Support Care Cancer. 2019; 27(9):3499-350
Disclosure Statement: C.Riese is employed by Cankado.
252
On-Site Integrative Oncology: The Bochum/Hattinger Model
André-Michael Beer 1, Stefanie Nöpel-Dünnebacke 2, Birke Müller 1
1Klinik für Naturheilkunde, Klinik Blankenstein, Hattingen, Katholisches Klinikum
Bochum GmbH, Hattingen, Deutschland
2Klinik für Hämatologie, Onkologie, Palliativmedizin, St. Josef-Hospital, Klinikum
der Ruhr-Universität Bochum, Bochum, Deutschland
Purpose: For the last 10 years, the Clinic for True Naturopathy in Hat-
tingen-Blankenstein has oered a consultation service for integrative
oncology tot he St. Josef-Hospital. Ruhr-University Bochum, department
of hematology and oncology. Since February 2019, aregular consultation
service on site, twice weekly, has been conducted.
Methods: From the 20th of February to the 26th of September, 2019,
N=154 male and female patients from the department of hematology and
oncology, St. Josef Hospital, Ruhr-University Bochum, were treated. e
diagnoses were: Pancreatic carcinoma (N=81), Breast carcinoma (N=7),
Lung carcinoma (N=12), Eophageal carcinoma (N=10), Stomac carci-
noma (N=2), Colon and Rectalcarcinoma (N=17), Ovarian carcinoma
(N=3), Others (N=22). In addition to a therapy program consisting of
the classical European natural healing remedies, to include phytotherapy,
wraps compresses and cupping therapy, acupuncture and mistletoe thera-
py (N=26) were also oered to suitable patients.
Results: First indications show that more patients can be recruited during
oncological patient visits by the presence of a qualied doctor of true na-
turopathy, thereby promoting the possibility for complementary naturo-
pathic treatment such as mistletoe therapy. In this period, mistletoe ther-
apy was discussed with N = 26 patients. Finally, N = 8 patients performed
mistletoe therapy.
Conclusions: Consultation between the oncologist and a medical special-
ist of true naturopathic treatment would identify suitable patients. e
therapy concept o he Bochum/Hattinger model is herewith presented.
Disclosure Statement: None
256
A Comparison of Physical Activity Change Patterns and
Determinants between Breast, Prostate and Colorectal Cancer
Patients
Johanna Depenbusch 1, 2; Alexander Haussmann 1, 3; Angeliki Tsiouris 4, 5;
Laura Schmidt 3; Silke Hermann 6; Monika Sieverding 3;
Joachim Wiskemann 4; Nadine Ungar 3; Karen Steindorf 1
1Abteilung Bewegung, Präventionsforschung und Krebs, Deutsches
Krebsforschungszentrum (DKFZ) und Nationales Centrum für
Tumorerkrankungen (NCT), Heidelberg, Deutschland
2Medizinische Fakultät Heidelberg, Universität Heidelberg, Heidelberg,
Deutschland
3Psychologisches Institut, Universität Heidelberg, Heidelberg, Deutschland
4Abteilung Medizinische Onkologie, Nationales Centrum für
Tumorerkrankungen (NCT) und Universitätsklinikum Heidelberg, Heidelberg,
Deutschland
5Klinik für Psychosomatische Medizin und Psychotherapie, Universitätsmedizin
der Johannes Gutenberg-Universität Mainz, Mainz, Deutschland
6Epidemiologisches Krebsregister, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Deutschland
Purpose: Despite well-established benets of physical activity (PA) for
cancer patients, a majority of patients do not meet recommended PA
guidelines (≥150 min moderate-to-vigorous PA/week). e purpose
of the study was to investigate how PA behavior changed from pre- to
post-diagnosis, which sociodemographic and medical factors were asso-
ciated with PA and how change patterns and determinants of PA diered
between breast, prostate and colorectal cancer patients.
Methods: In a cross-sectional study, 912 cancer patients (457 breast, 241
prostate, 214 colorectal cancer; on average 15.1 months post-diagnosis)
completed a questionnaire assessing sociodemographic and medical vari-
ables as well as their weekly duration of PA pre-diagnosis and within the
last week. PA change patterns and dierences between cancer types were
analyzed with non-parametric tests. Logistic regression analyses were
used to identify sociodemographic and medical determinants of sucient
post-diagnosis PA. Additionally, population subgroups more or less likely
to be physically active were detected using classication tree analyses.
Results: Despite a modest decrease of PA from pre- to post-diagnosis,
we found that 54% of cancer patients indicated to be suciently active
post-diagnosis. Considerable dierences in pre-diagnosis PA between
cancer types disappeared post-diagnosis. While for all cancer types,
post-diagnosis PA was strongly aected by pre-diagnosis PA, we detect-
ed dierences between cancer types regarding further PA determinants.
Our results suggest that previously inactive prostate cancer patients and
recently diagnosed patients currently undergoing cancer treatment had an
increased likelihood of being insuciently active post-diagnosis.
Conclusions: e number of suciently active cancer patients was en-
couragingly high. Yet it seems important to further raise awareness of PA
in the general population as well as in the post-diagnosis setting, where
interventions that are more tailored to specic patient and cancer charac-
teristics need to be established.
Disclosure Statement: e study was funded by German Cancer Aid. ere is no
conict of interest.
Prof. Dr. Karen Steindorf gibt folgende Verbindungen außerhalb des eingereichten
Abstracts an:
Personal fees from Pzer Pharmaceuticals (Consulting for writing a brochure on
physical activity and cancer for breast cancer patients), personal fees from Adviva
Heidelberg (Lecture Fee), non-nancial support from Asklepios Clinics (Travel
costs), personal fees from BIG direkt health insurance (Lecture fee, travel costs),
personal fees from TEVA Pharmaceuticals (Lecture fee, travel costs).
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294
Safety of a Combined Supervised and Home-Based Whole-
Body Vibration Intervention for Childhood Cancer Survivors
Vanessa Oschwald 1; Aram Prokop 2; Sarah Otten 1; Volker Maas 2;
Fiona Streckmann 1, 3; Wilhelm Bloch 1; Jonas Krumbach 1;
Julia Däggelmann 1
1Institut für Kreislauorschung und Sportmedizin, Deutsche Sporthochschule
Köln
2Kinderkrankenhaus Amsterdamer Straße, Kliniken der Stadt Köln gGmbH
3Departement für Sport, Bewegung und Gesundheit, Universität Basel
Purpose: To assess safety of a whole-body vibration (WBV) intervention,
combining supervised and home-based training for childhood cancer
survivors.
Methods: Eight childhood cancer survivors (mixed cancer types, age:
6-17) participated in a 12-week WBV-intervention, comprising one super-
vised and two home-based sessions per week. Training was performed on
a side-alternating vibration platform. WBV-protocol included one warm-
up (60 sec, 18 Hz, 2mm peak-to-peak amplitude) and 5-10 progressive
training exercises (60-90 sec, 18-27 Hz, 2mm peak-to-peak amplitude).
Adverse events leading to health deterioration and intervention drop out
were evaluated. Side eects of WBV were secondarily investigated.
Results: No study dropout due to WBV-related adverse events occurred.
ree patients reported pain in the feet following WBV (vibration fre-
quencies: 22Hz and 27 Hz) that required early training stop or temporary
training interruption. Itching in the feet and legs during exercising was
reported in almost all patients. One patient experienced itching in the
lower back.
Conclusions: Not only supervised1 but also home-based WBV is safe for
childhood cancer survivors. However, close monitoring seems necessary
to detect the onset of pain. Survivors and families should be informed that
common symptoms of WBV like itching2 are possible during or immedi-
ately following WBV.
References:
1. Rustler V, Prokop A, Streckmann F, et al. Whole-Body Vibration Training
Designed to Improve Functional Impairments Aer Pediatric Inpatient Anti-
cancer erapy: A Pilot Study. Pediatr Phys er 2018;30(4):341-394
2. Rittweger J, Beller G, Felsenberg G. Acute physiological eects of exhaustive
whole-body vibration exercise in man. Clin Physiol 2000;20(2):134-142
Disclosure Statement: No conicts to disclosure.
303
Real-World Evidence of the Eectiveness and Safety of
NEPA (Netupitant-Palonosetron) for the Prevention of
Chemotherapy-Induced Nausea and Vomiting (CINV)
in Patients (PTS) Receiving Highly (HEC) or Moderately
Emetogenic Chemotherapy (MEC): Final Results of a German
Prospective Non-Interventional Study
Meinolf Karthaus 2, Peter Klare 3, Gülten Oskay-Özcelik 4, Volker Heilmann 5,
Elke Wierick 6, Pia Wülng 7, Carsten Hielscher 8, Dagmar Guth 9,
Mark-Oliver Zahn 10, Claus Hanusch 11, Joachim Hesse 12, Peter Jungberg 13,
Christian Kurbacher 14, Ute Neef 15, Jörg Schilling 16
1Hämatologie und Onkologie, Klinikum Neuperlach, München, Deutschland
2Städtisches Klinikum München Neuperlach, München, Deutschland
3Praxisklinik Krebsheilkunde für Frauen/Brustzentrum , Berlin, Deutschland
4Praxisklinik Krebsheilkunde für Frauen/Brustzentrum, Berlin, Deutschland
5Praxis Günzburg, Günzburg, Deutschland
6Gynäkologisch Onkologischer Schwerpunkt Lohsa, OT Weißkollm, Deutschland
7Mammazentrum Hamburg am Krankenhaus Jerusalem, Hamburg, Deutschland
8g.SUND Gynäkologie Kompetenzzentrum, Stralsund, Deutschland
9Gynäkologische Praxis Plauen, Plauen, Deutschland
10Onkologische Kooperation Harz, Goslar, Deutschland
11Rotkreuzklinikum München Frauenklinik, München, Deutschland
12Praxis für Innere Medizin, Parchim, Deutschland
13Praxisklinik / Brustzentrum Chemnitz, Chemnitz, Deutschland
14Gynäkologisches Zentrum Bonn-Friedensplatz, Bonn, Deutschland
15Gemeinschaftspraxis für Innere Medizin, Hämatologie, Onkologie und
Gastroenterologie, Halle (Saale), Deutschland
16Praxisklinik / Brustzentrum Berlin, Berlin, Deutschland
Purpose: NEPA, the xed combination antiemetic composed of a neuroki-
nin-1 receptor antagonist (RA; netupitant) and a 5-hydroxytryptamine-3
RA (palonosetron), is recommended for CINV prophylaxis for HEC and
MEC. is prospective non-interventional study assessed quality of life
(primary endpoint), eectiveness and safety (secondary endpoints) of
NEPA in HEC/MEC-treated pts under real-world conditions. Here, we
report nal eectiveness and safety data by chemotherapy (CT) group.
Methods: Adult pts treated with 1- or 2-day (d) HEC or MEC receiving
NEPA per SmPC were enrolled. Eectiveness, including frequency and
severity of nausea and vomiting and use of rescue medication (RM), was
reported in pt diaries. Complete response (CR) was dened as no emesis
and no RM, and non-signicant nausea (NSN) as no or mild nausea. Ad-
verse events (AEs) were reported on d1–21 of each cycle (C). All data were
collected for 3 consecutive CT Cs.
Results: From 9/15 to 9/17, 2405 pts initially assessed at 162 centers across
Germany, of whom 2173 were analyzed. Median age was 58 y (range 25-
89); 85% were female and half of the pts had an ECOG of 0-1. Pts were
diagnosed with breast (66%), gastrointestinal (10%), ovarian (7%) or lung
(5%) cancer. More than half of the pts (1230, 56%) received anthracycline/
cyclophosphamide-(AC), 19% carboplatin-, 8% cisplatin-, 7% oxaliplatin-
and 9% other CTs. During the overall period in C1, CR rates were between
81-84% and comparable in the pt groups treated with dierent HEC or
MEC. NSN rates varied between over 73% in the carboplatin-, cisplatin-
and 45% in the oxaliplatin pt group, in the overall period in C1. Outcomes
were similar for C2 and C3. Overall, 7% of pts reported drug-related AEs,
with the most common (in >1% pts) being constipation, fatigue, insom-
nia, and nausea.
Conclusions: NEPA was highly eective at CINV control under re-
al-world conditions in AC-, carboplatin-, cisplatin-, oxaliplatin- and other
CT pts, with a predictable and favourable safety prole.
Disclosure Statement: Advisory Role, Honoraria: RIEMSER Pharma GmbH,
Helsinn Healthcare SA.
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313
Eects of a Whole-Body Vibration Intervention in Children
and Adolescents after Inpatient Anticancer Therapy on Ankle
Dorsiexion Function and Balance Control
Sarah Otten 1; Aram Prokop 2; Vanessa Oschwald 1; Volker Maas 2;
Fiona Streckmann 1, 3; Wilhelm Bloch 1; Jonas Krumbach 1;
Stefanie Willibald 1; Julia Däggelmann 1
1Institut für Kreislauorschung und Sportmedizin, Deutsche Sporthochschule
Köln, Köln, Deutschland
2Kinderkrankenhaus Amsterdamer Straße, Kliniken der Stadt Köln gGmbH, Köln,
Deutschland
3Departement für Sport, Bewegung und Gesundheit, Universität Basel, Basel,
Schweiz
Purpose: Ankle dorsiexion (DF) function (strength, range of motion
(ROM)) and balance control are oen impaired in children and adoles-
cents aer inpatient anticancer therapy. However, adequate functional ca-
pacity of the lower limbs is prerequisite for mobility and for being active
in general. Whole-body vibration (WBV) aims to improve those variables.
Methods: Eight children aer inpatient anticancer therapy (mixed diag-
noses, age: 6-17) participated in a twelve-week WBV intervention. Train-
ing was oered three times a week (1x supervised, 2x home-based). Train-
ing was performed on a side-alternating vibration platform. e training
sessions included one warm-up (60 sec, 18 Hz, 2mm peak-to-peak ampli-
tude) and 5-10 progressive training exercises (60-90 sec, 18-27 Hz, 2mm
peak-to-peak amplitude). Two testings were performed before and aer
the intervention assessing balance control (one-leg stance), ankle dorsi-
exor strength (hand-held dynamometry) and active DF ROM (measured
with bent and straight legs, goniometry).
Results: Positive trends were reported in balance control, strength of an-
kle DF and active ankle DF-ROM with straight legs. Active DF-ROM with
bent legs was signicantly improved.
Conclusions: e results indicate that our WBV-intervention, combin-
ing supervised and home-based training sessions, can improve all of the
three focused parameters, especially active DF-ROM. Consequently, the
barriers for a regained higher level of physical activity can be consider-
ably reduced. WBV might be a promising modality to improve lower limb
function in pediatric oncology.
Disclosure Statement: e authors have no conicts to disclosure.
314
Lung Cancer Patients’ Expectations and Support Needs
Regarding Patient Navigation
Hella Fügemann 1; Ute Goerling 2; Kathrin Gödde 3; Nina Rieckmann 3;
Jacqueline Müller-Nordhorn 4; Christine Holmberg 5
1Institut für Public Health, Charité – Universitätsmedizin Berlin, Berlin,
Deutschland
2Charité Comprehensive Cancer Center , Charité – Universitätsmedizin Berlin,
Berlin
3Institut für Public Health, Charité – Universitätsmedizin Berlin, Berlin
4Bayerisches Krebsregister, Bayerisches Landesamt für Gesundheit und
Lebensmittelsicherheit
5Institut für Sozialmedizin und Epidemiologie, Medizinische Hochschule
Brandenburg Theodor Fontane
Purpose: Lung cancer patients face a low ve-years-survival rate.1 Due
to this poor prognosis, treatment with palliative intent is oen initiated
early aer diagnosis. Navigation programs for patients aim to optimize the
individuals care trajectory including early integration of palliative care,
which has positive eects on patients’ quality of life.2 In Germany, there is
little coordination of a patient`s continued care and patient navigation is
only slowly evolving. In this study, we investigated lung cancer patients`
perspectives on patient navigation.3
Methods: A longitudinal interview study was conducted with 20 lung
cancer patients assessed at three time points (aer diagnosis, at 3-6 and at
6-12 months). e interviews were audio-recorded and transcribed verba-
tim. We conducted a thematic analysis.
Results: Navigation needs were mainly seen in emotional and practical
support, but also in linking patients to existing support services and pro-
viding information on social care issues. Patients would appreciate the
continued support through one contact person. For navigation to be of in-
terest to patients its implementation within existing care structures, such
as the outpatient clinic or oncology practice, is crucial.
Conclusions: From the patients` perspectives, navigation could be a sup-
portive approach to identify and address their individual healthcare needs
and improve their journey through the complex care continuum by hav-
ing one permanent contact person.
References:
1. Krebs in Deutschland 2013/2014: Robert Koch-Institut, GEKID e.V.,
2017
2. Temel JS, et al. Early palliative care for patients with metastatic non-small-cell
lung cancer. N Engl J Med 2010
3. Fügemann H, et al. Patienten-Navigation – Erwartungen, Bedarfe und Anfor-
derungen aus Patientenperspektive. DKVF. Berlin 2019
Disclosure Statement: is work is part of the research consortium
“NAVICARE – Patient-oriented health services research. NAVICARE is
funded by the German Ministry of Education and Research (01GY1601).
316
Patient Information, Communication and Competence
Empowerment in Oncology (PIKKO) – Evaluation of a
Supportive Care Intervention for Overall Oncological Patients:
Baseline Data and Representativeness
Nico Schneider 1; Anna Bäcker 1; Katja Brenk-Franz 1; Christian Keinki 2;
Jutta Hübner 3; Florian Brandt 4; Geraldine von der Winkel 4; Lutz Hager 5;
Bernhard Strauß 1; Uwe Altmann 1
1Institut für Psychosoziale Medizin und Psychotherapie, Universitätsklinikum
Jena, Jena, Deutschland
2Deutsche Krebsgesellschaft, Berlin, Deutschland
3Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum
Jena, Jena
4IKK Südwest, Saarbrücken, Deutschland
5ze:roPraxen, Schwetzingen, Deutschland
Purpose: In Saarland the supportive new consulting and information
path, called PIKKO (funded by InnoFond, 01NVF17011), is implemented
for all types of cancer. e evaluation study is still ongoing. e study
design is presented, the participating patients are described and their rep-
resentativeness discussed.
Methods: We included all cancer types (new diseases and existing ones)
and used a non-randomized, comparative, multicenter superiority design.
e patients assigned to a control group (usual care) or intervention group
(usual care + PIKKO). e core elements of intervention are a patient nav-
igator, oncological knowledge database, and specialized psycho-oncolog-
ical counseling. In addition to patient surveys, data from statutory health
insurances and usage data from the web database are collected, and inter-
views with patient navigators and doctors are carried out.
Results: Recruitment will be completed in October 2019. Preliminary de-
mographic analyzes indicated that the PIKKO sample is broadly similar to
other German cancer studies [1, 2, 3]. e score ranges for quality of life,
depression and anxiety are comparable to Gotze [1] and Sauer [2], but a
little more distressed. Dominant cancer types are breast cancer (C50), leu-
kemia and lymphoma (C81-C96) and lung cancer (C33-C34). Final data
will be available at time of the congress.
Conclusions: PIKKO is designed to improve quality of life, self-ecacy,
health literacy and patient satisfaction and to reduce psychological dis-
tress, related health care costs and the days of inability to work.
References:
1. Gotze H. [Psychosocial Situation and Patient Satisfaction among Clients of
Cancer Counselling Centers in Saxony]. Psychother Psychosom Med Psychol
2016.
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2. Sauer Cl. Impact of social support on psychosocial symptoms and quality of
life in cancer patients … Acta oncologica 2019.
3. Hartung TJ. e risk of being depressed is signicantly higher in cancer pati-
ents than in the general population... Eur J Cancer 2017.
Disclosure Statement: No competing interests.
321
Assessment of Body Composition with Dierent Methods in
Breast Cancer Patients
Monika Reuss-Borst 1, 2; F. Joos 2; U. Kämmerer 3
1Rehabilitation-Center Bad Bocklet, Deutschland
2University of Göttingen
3Dpt. Of Gynecology and Obstetrics, University of Würzburg
Purpose: Many studies have consistently shown that malnutrition is asso-
ciated with higher degrees of treatment-related toxicity, reduced response
to cancer treatment and worse prognosis. In particular, body mass index
may be normal in patients with sarkopenic obesity. So far, screening for
malnutrition, in particular the assessment of body composition is still the
exception in daily practice although dierent well-established techniques
of body composition analysis do exist.
Methods: In this study body composition of 92 breast cancer patients was
analyzed at t0 and aer 20 weeks. Dierent methods such as bioelectri-
cal impedance analysis (BIA), near-infrared interactance (NIR) and dual
x-ray absorptiometry (DXA) (considered as the current gold standard) as
well as a simple body fat scale (BFS) from the discounter were compared
with respect to various outcome variables (e.g. fat mass (FM), fat free mass
(FFM) etc.), their validity and reliability as well as costs and handling.
Results: DXA, BIA and NIRS yielded similar results for body compo-
sition, including FM (DXA: 28,9 BIA: 28,2 kg, NIRS: 27,9kg) and FFM
(DXA: 44,5kg, BIA: 46,2kg, NIRS: 46,5kg). Results, however, diered sig-
nicantly between these 3 methods and a simple BFS (FM: 22kg, FFM:
50,0kg), which overestimated fat free mass and underestimated fat mass
(p<0,01). With regard to changes in body composition over time, all 4
investigated methods yielded comparable results (FM p=0,698 resp. FFM
p=0,211).
Conclusions: All investigated methods are suitable for follow-up checks
in oncological patients when monitoring changes in body composition
over time. is even applies for a simple body fat scale which, however,
signicantly overestimates FFM and underestimates FM in comparison
to the other techniques. For the exact measurement of body composition
NIR and BIA are rapid, safe, non-invasive and inexpensive techniques
with valid and reliable results - ideal for routine body composition as-
sessment.
338
Physical Fitness and Body Composition in Breast Cancer
Patients that Adhere to Dierent Nutritional Regimes
Monika Reuss-Borst 1, 2; T. Schäfer 2; U. Kämmerer 3
1Center for Rehabilitation and Prevention Bad Kissingen/Bad Bocklet
2University of Göttingen
3Dept. of Obstetrics and Gynecology, University of Würzburg
Purpose: Breast cancer (BC) patients are oen advised to adhere to a
“healthy diet. However, this diet has not been dened yet. e aim of this
study was to evaluate the eect of three dierent diets on physical tness
and body composition.
Methods: 152 BC patients could choose between 3 diets. ey received in-
tense training and advice during 3 wks of rehabilitation and were instruct-
ed to adhere to their diet for 20 weeks in total. Proportion of macronutri-
ents in energy percent (fat/protein/carbohydrates) were: Ketogenic diet
(KD) 80/16/4 (n = 29), Low-Carb diet (LC) 50/20/30 (n = 92) and western
diet (WD) 30/15/55 (n = 31). Dual-Energy x-ray (DXA) and spiroergom-
etry were performed at start (t0) and aer 20 weeks (t20) to analyse body
composition and physical tness. Data were analyzed by non-parametric
Kruskal-Wallis test or Mann-Whitney-U-Test.
Results: From t0 to t20 muscle/fat ratio increased [2.1/2.4 (KD), 1.6/1.77
(LC) (p=0.02) and 1.65/1.75 (WD)] and visceral fat decreased [10.0/7.9kg
(KD), 14.3/12.6kg (LC) and 12.7/12.1 (WD)] in all diet groups. At t0, to-
tal fat was lowest with KD (21.8kg) (p<0.001) and the muscle/fat relation
(2.3) was signicantly higher than with LC (1.8) and WD (1.9). Subgroup
analysis based on food questionnaires revealed, that 14/31 patients had
used KD, 8/31 LC and only 7/31 WD before the study while 14/92 in the
LC group hat used LC before and the 31/31 patients of the WD group
started from WD.
With regard to physical tness, both, Vo2/kg at VT2 (anaerobic
threshold) [KD (+2.93), LC (+0.64) and WD (+0.48]) and Vo/kg Max [KD
(+2.51), LC 1.43 and WD(+2,49)] increased between t0 and t20.
Conclusions: All 3 groups improved in body composition and physical
tness attesting the ecacy of the rehabilitation intervention. However,
KD proved to be best for positive changes in muscle/fat ratio and physical
tness. One reason of this surprising result might be that ketone bodies
may act as “super fuel” improving energy eciency which is especially
important in cancer patients.
e therapeutic potential of a KD as nutritional regime should be fur-
ther evaluated.
390
Phytotherapeutic Approaches for Treating Mucositis, Loss of
Appetite, Xerostomia and Ageusia –An Analysis of Empirical
Knowledge
Judith Büntzel 1; Christoph Bauer 2; Jens Büntzel 3
1Klinik für Hämatologie und Onkologie, Universitätsmedizin Göttingen,
Görringen, Deutschland
2Medizinische Klinik III, Klinikum Fulda, Fulda, Deutschland
3Klinik für HNO-Erkrankungen, Kopf-Hals-Chirurgie, Südharz-Klinikum
Nordhausen, Nordhausen, Deutschland
Purpose: Which empirical reports can be found regarding phytothera-
peutics used traditionally to treat lack of appetite and dysphagia?
Methods: We screened 10 German books on phytotherapy for the follow-
ing symptoms: mucositis/stomatitis/gingivitis, anorexia/loss of appetite,
xerostomia and loss of taste. All traditional European herbs were includ-
ed. Hits were registered on an Excel spreadsheet.
Results: We found 133 plants; 103 are recommended for treating oral mu-
cositis, 75 for stimulating appetite, 10 for alleviating xerostomia and for
stimulating taste. Matricaria chamomilla L., Salvia ocinalis L. and the
bark of Quercus robur L. are the most commonly mentioned herbs for
treating mucositis. e following herbals were the most frequently recom-
mended as stimulants of appetite: Artemisia absinthium L., Centaurium
Hill and Cichorium intybus L.. Zingiber ocinale Roscoe, Gentiana lutea
L. und Centaurium Hill were mentioned several times as potent agents to
alleviate xerostomia. Gentiana lutea L. might be also used to treat ageu-
sia. Gentiana lutea L. is qualied to treat all four symptoms investigated;
Angelica archangelica L., Zingiber ocinale Roscoe, Cuminum cyminum L.
and Centaurium Hill are recommended for treating three out these.
Conclusions: Here we summarize a canon of the 10 plants recommended
by traditional (European) medicine.Clinical studies are required to inves-
tigate their therapeutic ecacy against mucositis, anorexia, xerostomia
and ageusia.
Disclosure Statement: e authors declare no conict of interest.
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405
Reduction of Severity of Chemotherapy-Induced Peripheral
Neuropathy by Onlife: Final Results of the Breast Cancer
Cohort of the Stefano Trial
Matthias Zaiss 1; Jens Uhlig 2; M.-O. Zahn 3; Thomas Decker 4;
Helmar Lehmann 5; Johanna Harde 6; Cathrin Hogrefe 6; Corinne Vannier 6;
Norbert Marschner 1, 6
1Praxis für interdisziplinäre Onkologie & Hämatologie GbR, Freiburg im
Breisgau, Deutschland
2Praxis Dr. med. Jens Uhlig, Naunhof, Deutschland
3Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation
Harz, Goslar, Deutschland
4Studienzentrum Onkologie Ravensburg, Ravensburg, Deutschland
5Universitätsklinikum Köln (AöR), Köln, Deutschland
6iOMEDICO AG, Freiburg im Breisgau, Deutschland
Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a
common and potentially dose-limiting side eect of neurotoxic chemo-
therapy, especially of platinum and taxanes, with a profound impact on
patients (pts)’ quality of life and survivorship. It is predominantly caused
by sensory axon damage. ere is no eective strategy to prevent or cure
CIPN. OnLife®, a patented mixture of fatty acids (F.A.G.®) with the main
component palmitoylethanolamide (PEA), is supposed to have anti-in-
ammatory, neuroprotective and antinociceptive properties.
Methods: STEFANO is an observational, prospective, two-cohort, mul-
ticenter study designed to evaluate the inuence of OnLife® on existing
CIPN in adult pts with colon or breast cancer aer neo-/adjuvant che-
motherapy (cohort A: colon cancer, oxaliplatin-based therapy; cohort B:
breast cancer, paclitaxel therapy). Pts received OnLife® orally BID for 3
months. Neuropathy assessment before, during and aer OnLife® intake
included physical examination and neurophysiological testing, i.e. tendon
reexes, vibration sensitivity and CIPN grading according to CTCAE
v4.03. e primary objective was the change in severity of CIPN (CT-
CAE v4.03) before and aer 3 months of OnLife® intake. Secondary end-
points included Patient-reported outcomes (PROs; EORTC QLQ-C30,
-CIPN20). Descriptive statistics were used to analyze data.
Results: In total, 74 breast cancer pts with paclitaxel-induced CIPN re-
ceived OnLife®. According to CTCAE, aer OnLife® intake 31% of pts had
an improvement of sensory CIPN, 54% of pts experienced a stabilization,
with no further worsening, 1% of pts had a deterioration and 14% of pts
were not evaluable. In pts with grade 2/3 sensory CIPN (n=58), 36% had
an improvement, 50% a stabilization and no deterioration occurred. Ac-
cording to PROs, 45% of pts had less symptoms and functional limitations
related to sensory CIPN aer OnLifeâ intake.
Conclusions: OnLife® may reduce the severity of existing CIPN in breast
cancer pts treated with paclitaxel and thus appears to be a promising treat-
ment option for CIPN.
458
Administration of Peglgrastim Prophylaxis Via Pre-Filled
Syringe (Neulasta®) or On-Body Injector (OBI): Interim
Results on Patient Preference and Health Economics from the
Convenience Study
Michael Metz 1; Dieter Semsek 2; Ulrich Hutzschenreuter 3; Thomas Fietz 4;
Johanna Harde 5; Stefan Zacharias 5; Gunther Rogmans 6;
Carsten Hielscher 7; M.-O. Zahn 8; Christiane Fichter 5; Sina Grebhardt 5;
Gerlinde Egerer 9; Karin Pottho 5
1OPS Göttingen, Göttingen
2Praxis für interdisziplinäre Onkologie & Hämatologie GbR, Freiburg im
Breisgau, Deutschland
3Hämatologisch-Onkologische Gemeinschaftspraxis, Hämatologisch-
Onkologische Gemeinschaftspraxis, Nordhorn, Deutschland
4Schwerpunktpraxis für Hämatologie und Internistische Onkologie,
Gastroenterologie, Singen (Hohentwiel), Deutschland
5iOMEDICO AG, Freiburg im Breisgau, Deutschland
6ZAGO - Zentrum für ambulante gynäkologische Onkologie, Krefeld,
Deutschland
7g.SUND Gynäkologie Kompetenzzentrum Stralsund, Stralsund, Deutschland
8Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation
Harz, Goslar, Deutschland
9Universitätsklinikum Heidelberg, Medizinische Klinik und Poliklinik V,
Heidelberg, Deutschland
Purpose: e eectiveness of granulocyte colony-stimulating factors
(G-CSFs) like peglgrastim depends on the optimal timing, recommend-
ed ≥24 h aer chemotherapy (CTx) according to SmPC and guidelines.
Return visits to the medical oce for peglgrastim administration, how-
ever, may be burdensome and cause additional expenditure of time and
costs for both, patients and medical sta.
e peglgrastim On-body injector (OBI) is a small injector automati-
cally delivering a subcutaneous peglgrastim dose aer 27 h without need
of return visit to the medical oce. erewith the OBI has the potential
to optimize peglgrastim prophylaxis. e CONVENIENCE study aims
to evaluate patient’s preference and health economics for peglgrastim
administration via OBI versus pre-lled syringe (PS) in real-world in
Germany.
Methods: In this randomized, multicenter study (partially funded by
AMGEN GmbH) 400 patients with early breast cancer receiving 2 or 3
weekly anthracycline/cyclophosphamide or 3 weekly taxane-based CTx
or patients with Non-Hodgkin lymphoma receiving 1st-line R-CHOP-14
or-21 will be enrolled at 50 sites in Germany. Patients are observed for
4 CTx cycles supported with peglgrastim OBI or PS in an alternating
sequence with 1:1 randomization of the application form to start with.
Patient’s preference and inuence of peglgrastim administration on daily
life and cost factors will be evaluated using patient surveys.
Results: For this prespecied interim analysis, 200 patients were random-
ized between 06/2018 and 01/2019. Data on patient characteristics, time
interval between CTx and peglgrastim administration, patient’s prefer-
ence before and aer study including reasons for decision and inuence of
the dierent application forms on daily life (daily routine, social life, time
restriction) and health economics will be presented.
Conclusions: e results of the interim analysis demonstrate the feasibil-
ity, eectiveness and convenience of administering peglgrastim via OBI.
Reference:
1. Metz M et al, DGHO 2019, P944.
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462
Motivation for an Active Lifestyle (Motiva) – Pilot Study of
a Behavior-Change Module in Exercise Programs for Cancer
Survivors
Melanie Glausch 1; Friederike Stölzel 1; Nadja Seidel 1; Anne Fetzer 1;
Vera Fieber 1; Bornhäuser Martin 1, 2, 3; Nadine Ungar 4; Joachim
Wiskemann 5
1Universitätsklinikum Carl Gustav Carus Dresden, Universitäts Krebscentrum
(UCC), Dresden, Deutschland
2Universitätsklinikum Carl Gustav Carus Dresden, Medizinische Klinik und
Poliklinik I, Dresden, Deutschland
3Nationales Centrum für Tumorerkrankungen (NCT), Dresden, Deutschland
4Ruprecht-Karls-Universität Heidelberg, Psychologisches Institut
Genderforschung und Gesundheitspsychologie, Heidelberg, Deutschland
5Medizinische Onkologie, Universitätsklinikum Heidelberg, Nationales Centrum
für Tumorerkrankungen (NCT), Heidelberg, Deutschland
Purpose: Physical Activity (PA) is associated with many benets for
cancer survivors (CS).1 However, research has shown insucient levels
of PA for CS. Rehabilitation sport groups (RSG) are a common way to
deliver exercise interventions to CS in Germany but measures to increase
sustainability of PA aer the end of RSG are still lacking. erefore, the
National Center for Tumor Diseases (NCT)/UCC Dresden and the NCT
Heidelberg developed a behavior-change program (MotivA) as additional
module for existing RSG.
Methods: MotivA teaches behavior-change-techniques (e.g. action-plan-
ning and coping) based on the Health Action Process Approach. MotivA
is an additional module that can be used in CS groups. A project kit free
of charge consists of a manual for trainers (incl. a CD with 7 audio-inputs)
and a workbook for CS. A pilot-study with a pre-post-3 month-follow-up
(FU) design without control group investigates the eects of MotivA on
subjective PA, motivational determinants of PA and program acceptance
with 29 participants.
Results: 76% of the participants were pleased with the additional behav-
ior-change module being part of the exercise program. At baseline, 62% of
the participating patients reported insucient PA. Motivational barriers
as ‘Can’t pick myself up’ (47%), ‘Not in the mood’ (33%) and ‘Comfortable
at home’ (33%) and ‘Bad weather’ (32%), were most frequent. Pre-post
dierences show a signicant increase in subjective reported PA levels
(p<.01, r=.61) and a signicant decrease of motivational barriers (p < .01,
r = .49). e eects in increased subjective PA and reduced motivational
barriers remained stable at 3 months-FU.
Conclusions: e results of this pilot-study are promising that MotivA
can support CS in developing a more active lifestyle. MotivA can be easily
disseminated and integrated in any exercise program for CS.
Reference:
1. Christensen, J. F., Simonsen, C. & Hojman, P. (2018). Comprehensive Physio-
logy, 9(1):165-205.
Disclosure Statement: No conicts of interest.
494
Dening Criteria for Guiding Cancer Patients to Find a
Reputable Complementary Medicine Provider: Results of a
Mixed-Methods Study
Alize Rogge 1; Isabel Baur 2; Gabriele Blettner 3; Ulrike Holtkamp 4;
Markus Horneber 5; Patrick Jahn 6; Stefanie Joos 7; Silva Keberle 8;
Anita Kettelgerdes 9; David Klemperer 10; Alfred Längler 11; Petra Voiß 12, 13;
Joachim Weiß 14; Claudia Witt 1, 15, 16
1Charité Universitätsmedizin Berlin Campus Benjamin Franklin, Institute for
Social Medicine, Epidemiology, and Health Economics, Berlin, Deutschland
2Universität Zürich, Competence Center Medicine Ethics, Zürich, Schweiz
3Deutsche Krebshilfe, INFONETZ KREBS, Bonn, Deutschland
4Deutsche Leukämie- und Lymphom-Hilfe, Bonn, Deutschland
5Paracelsus Medizinische Privatuniversität Nürnberg, Department of Internal
Medicine, Nürnberg, Deutschland
6Universität Halle, Nursing Research Unit, Halle (Saale), Deutschland
7Universitätsklinikum Tübingen Medizinische Universitätsklinik, Institute for
General Practice and Interprofessional Health Care, Tübingen, Deutschland
8Eskamed AG, Basel, Schweiz
9TK Techniker Krankenkasse, Buchen, Deutschland
10Ostbayerische Technische Hochschule Regensburg (OTH Regensburg), Faculty
of Social and Health Sciences, Regensburg, Deutschland
11Gemeinschaftskrankenhaus Herdecke, Institute of Integrative Medicine,
Herdecke, Deutschland
12Kliniken Essen-Mitte Evang. Huyssens-Stiftung, Clinic for Naturopathy and
Integrative Medicine, Essen, Deutschland
13Städtisches Klinikum Karlsruhe gGmbH, Gynaecology Clinic, Karlsruhe,
Deutschland
14Uniklinik Freiburg - Klinik für Tumorbiologie, Department of Psychooncology,
Freiburg im Breisgau, Deutschland
15Universität Zürich, Institute for complementary and Integrative Medicine,
Zürich, Schweiz
16University of Maryland School of Medicine Department of Neurology, Center
for integrative Medicine, Baltimore, United States
Purpose: Approximately half of cancer patients use complementary med-
icine(CM) during their cancer treatment[1]. However, even in cases of
positive evidence for CM therapies [2], it is still dicult for cancer pa-
tients to identify reputable CM providers on their own. e aim of this
study was to develop and evaluate a criteria list to provide guidance to
cancer patients seeking a reputable CM provider.
Methods: In this mixed-methods study, results of a systematic literature
review, a multi-level expert consensus procedure (n=15) and a practice
evaluation from three relevant stakeholder perspectives (cancer patients
(n=18), CM providers (n=26) and oncology physicians (n=20)) were
combined.
Results: A total of 30 CM criteria were extracted from the literature, and
12 more were added by the experts. All criteria were assigned in their
importance for cancer patients to nd reputable providers, oncology phy-
sicians to establish a CM provider network and registers for quality assur-
ance in nonmedical CM providers. A nal comprehensive list of 8 criteria
guiding cancer patients to nd a reputable CM provider was developed in
the form of a leaet.
Conclusions: Health professionals and cancer information services might
nd the criteria list helpful when aiming to strengthen patients’ awareness
of quality-related factors associated with nonmedical CM providers. e
criteria developed might support the development of standards for quality
assurance in CM in oncology.
References:
1. Horneber, M., et al., How many cancer patients use complementary and alterna-
tive medicine: a systematic review and metaanalysis. Integr Cancer er, 2012.
11(3): p. 187-203.
2. Lyman, G.H., et al., Integrative erapies During and Aer Breast Cancer Treat-
ment: ASCO Endorsement of the SIO Clinical Practice Guideline. J Clin Oncol,
2018. 36(25): p. 2647-2655.
Disclosure Statement: We declare no competing interests. is project is part of
the collaborative research project KOKON supported by the German Cancer Aid
[grant number 109863].
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An Interdisciplinary Outpatient Clinic for Patients with
Neurological Sequelae of Cancer Therapies – Results of a Pilot
Project at the University Hospital of Bonn
Johannes Weller1, Maria Vonnahme2, Martin Schumacher2, Judith Sirokay3,
Tobias Holderried2, Ulrich Herrlinger1, Niklas Schäfer1
1Universitätsklinikum Bonn, Sektion Neuroonkologie, Bonn, Deutschland
2Universitätsklinikum Bonn, Medizinische Klinik III (Onkologie), Bonn,
Deutschland
3Universitätsklinikum Bonn, Klinik für Dermatologie, Bonn, Deutschland
Purpose: Most patients with cancer experience adverse events aer on-
cological treatment. Neurological sequelae are among the most important
challenges in patient survivorship, including but not limited to muscle
weakness, neuropathic pain, gait disorders and cognitive impairment,
which oen have a signicant impact on activities of daily life. To improve
diagnosis and treatment of these side eects, we started a pilot project for
cancer patients with neurological symptoms.
Methods: A consultation service for cancer patients was on a trial basis
implemented at the Division of Clinical Neurooncology. Consultations
were requested via the clinical workstation used at a tertiary universitary
medical center. Necessary information was a short description of symp-
toms, the assumed diagnosis and the priority in time. Contact was also
possible by phone call of selected collaborators. Our experience of the pi-
lot project was analysed in a descriptive manner.
Results: Between October 2018 and July 2019, a total of 42 patients with
65 visits were evaluable. e most frequent question was dierentiation
between chronic gra-versus-host-disease and neuropathy or myopathy
(40,5%). e leading neurological diagnosis was peripheral neuropa-
thy (42,9%). In 76,2% of the cases the neurological consultation led to
additional examinations and in 71,4% of the cases the consultation had
therapeutic implications. Usage of antiepileptic drugs or antidepressants
to modify neuropathic pain was recommended in 16,7% of the cases. 17
patients had at least one follow up visit within the reported period. Suc-
cessful treatment with improvement of symptoms was shown in 35,3% of
patients with follow-up visits.
Conclusions: ere seems to be a formerly unmet demand of neurologi-
cal consultation service in neurological sequelae of cancer therapies that
can be supplied by a specialized outpatient clinic. Building on the expe-
rience of this pilot project, a special outpatient clinic will now be perma-
nently established at our Division of Clinical Neurooncology.
505
Onkoaktiv-Network Evaluation: A Patient’s Perspective
Annelie Voland; Joachim Wiskemann
Nationales Centrum für Tumorerkrankungen – NCT, Medizinische Onkologie,
Heidelberg, Deutschland
Purpose: More than 700 RCTs have shown signicant positive eects of
exercise interventions for cancer patients and survivors; as well as clinical
relevant decreases in mortality rates through exercise behavior 1. Howev-
er, there is no comprehensive provision of exercise therapy in the German
medical system. erefore, OnkoAktiv follows the idea of building a net-
work, consisting of exercise professionals, training- and cancer treatment
centers, to connect patients with quality assessed and certied exercise
oers. e purpose of the project was to evaluate the work of OnkoAktiv
from a patient’s perspective.
Methods: Patients are recruited through OnkoAktiv at the National Cen-
ter for Tumor Diseases in Heidelberg. Evaluation consists of three assess-
ment time points (Q1: patient´s rst consultation, Q2: completed con-
nection to training facility, Q3: 8 weeks of exercise therapy) measuring
QoL, self- ecacy, volume of exercise, satisfaction, structure and process
quality parameters of the OnkoAktiv service and supervision by exercise
professionals.
Preliminary Results: By now, 71 of 86 patients with an average age of 56
years (SD=11.52) are enrolled, of which 59 already completed Q1 and 25
Q3. e distribution presents 26 patients with breast-, 19 with prostate-
and 20 with other cancer types. e mean time for patient´s placement
in an exercise facility was 38 days, serving 37 dierent exercise facilities
within the Rhein-Neckar-Region. 35 out of 55 participants already report-
ed high satisfaction in rating the OnkoAktiv service; however training
volume seems to be demanding during treatment and needs to be adjusted
on a day to day basis. 14 patients dropped out aer enrolment. Recruit-
ment will be completed in Oct 2019, data analysis will be nalized Dec
2019.
Conclusions: is study is the starting point of the OnkoAktiv-network
evaluation for further research in the eld of oncological exercise therapy.
Reference:
1. Christensen et al. (2018): Exercise Training in Cancer Control and Treatment.
In: Comprehensive Physiology 9 (1), S. 165–205.
Disclosure Statement: None
536
Eects of Physical Activity on Sexual Dysfunction in
Urooncological Patients – A Systematic Review
Nadine Reimer 1; Rebecca Böwe 2; Freerk Baumann 1
1University of Cologne, University Hospital of Cologne, Department I of Internal
Medicine, Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf,
Köln, Deutschland
2Hochschule Fresenius, Faculty of Health and Social, Köln, Deutschland
Purpose: Many therapies performed as part of cancer treatment cause
sexual dysfunction as a side eect, which can occur, for example, as impo-
tence (up to 57%) and impaired sexual desire (up to 78%). Data show that
a higher activity level in urooncological cancer patients is associated with
better sexual health. is systematic review aimed at demonstrating the
ecacy of exercise interventions for sexual dysfunction in urooncological
patients.
Methods: A systematic data search was performed in PubMed in May
2019. In addition, the reference lists of individual publications were
screened. e review was undertaken according to the Preferred Report-
ing Items for Systematic Reviews and Meta-Analyses (PRISMA) state-
ment.
Results: e current status of the paper may change until the Congress
in February 2020. e systematic review currently includes 24 studies (16
RCTs, 1 non-RCT, 4 single-arm trials, 1 interview, 1 case report, 1 case
series) involving approximately 1605 cancer patients. e studies involved
prostate cancer (20), endometrial cancer (1), cervical cancer (1), gynae-
cological cancer (1), gynaecological and other cancers (1). e exercise
interventions were performed individually or in combination with other
interventions such as electrostimulation, nutrition or cognitive training.
For prostate cancer, erectile and sexual function, potency, and libido im-
prove (partly signicantly) by performing pelvic oor muscle exercise
(PFME), resistance and aerobic exercise, yoga and penile vibratory stim-
ulation compared to control group. For women, PFME, Pilates, resistance
and aerobic exercise show (partly signicantly) positive eects on sexual
activity and sexual function.
Conclusions: e rst set of data shows positive eects of exercise inter-
ventions on urooncological patients. is requires further studies.
Reference:
with the main author
Disclosure Statement: ere are no conicts of interest.
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2018
539
Patient Information, Communication and Competence
Empowerment in Oncology (PIKKO) – A Supportive Care
Intervention for Oncological Patients
Christian Keinki 1; Katrin Clauß 1; René Meyer 1; Annika Momberg 1;
Robert Terbach 1; Nico Schneider 2; Anna Bäcker 2; Florian Brandt 3;
Geraldine von der Winkel 3; Lutz Hager 4; Bernhard Strauß 2; Uwe Altmann 2;
Jutta Hübner 5
1Deutsche Krebsgesellschaft e.V., Projekt PIKKO, Berlin, Deutschland
2Universitätsklinikum Jena, Institut für Psychosoziale Medizin und
Psychotherapie, Jena, Deutschland
3IKK Südwest, Saarbrücken
4ze:roPRAXEN GbR, Schwetzingen, Deutschland
5Universitätsklinikum Jena, Klinik für Innere Medizin II, Jena, Deutschland
Purpose: In German healthcare, cancer patients are faced with confusing
care structures and an inadequate integration of psychosocial and infor-
mative support services. For this reason, a new care concept, called PIKKO,
is tested in the Saarland.
PIKKO is a collaborative project which is funded by the Innovation
Fund. Consortium partners are German Cancer Society, Cancer Society
of the Saarland, University Hospital Jena, IKK Südwest, Techniker Kran-
kenkasse (TK), and Knappscha.
Methods: Core elements of PIKKO are patient navigators, which accom-
pany cancer patients on their way through their therapy. In addition,
patients can access quality-assured information at any time via an exclu-
sively created oncological knowledge database and can take advantage of
specialized psychosocial counselling services.
All cancer types were included. Patients were either assigned to a
control group (usual care) or intervention group (usual care + PIKKO).
We used patient surveys to evaluate all patient related outcomes. Health
care costs were analyzed with data from participating statutory health
insurances.
Results: Main goal is to empower patients to deal with their disease in
a well-informed and autonomous manner. In measurable terms, PIKKO
should lead to a better quality of life, self-ecacy, health literacy and sat-
isfaction with healthcare. At the same time there should be a reduction of
psychological stress and costs of care.
Overall 15 patient navigators were deployed. Recruitment of patients
for the control group is completed. e intervention group is recruiting
until March 2020.
Conclusions: PIKKO is intended to become a well-established and benet
assessed program which improves care of all cancer patients in Germany.
Disclosure Statement: No competing interests.
550
Safety and Eectiveness of Sensor-Controlled Scalp Cooling
to Prevent Chemotherapy-Induced Alopecia in Patients with
Ovarian and Other Female Genital Tract Cancers
Christian M. Kurbacher 1; Nele Kettelhoit 1; Susanne Herz 1;
Gabriele Kolberg 1; Claudia Schweitzer 1; Jutta Anna Kurbacher 2
1Gynäkologisches Zentrum Bonn-Friedensplatz, Bonn
2Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie II (Allgemeine
Gynäkologie und Geburtshilfe), Bonn
Purpose: In prospective clinical trials, sensor-controlled scalp cooling
(SCSC) has been found to eectively reduce the risk of CIA in patients
(pts) exposed to Ctx for early breast cancer. However, data on SCSC in pts
with female genital tract cancer are largely lacking.
Methods: 44 pts with various female genital tract cancers who underwent
SCSC alongside to CIA-inducing Ctx were included. 35 pts had epithe-
lial ovarian and related carcinomas (79.5%), the remainder (20.5%) had
various other malignancies, mainly cervical cancer. 18 pts (40.9%) were
treated in a curative intent, 26 pts (59.1%) received palliative Ctx. 24 pts
(54.5%) had been previously exposed to Ctx. Pts were subjected to SCSC
during each Ctx cycle. CIA was quantied according to the Dean score
(DS) 3 wks aer the last Ctx cycle. Data were analyzed regarding feasibility
indicated by the SCSC completion rate, quality of hair preservation (suc-
cess: DS 0-2, failure: DS 3-4), reasons of SCSC discontinuation, and safety.
Results: 31 pts (70.5%) completed SCSC. e reasons for discontinuation
were CIA in 10 (22.7%) and adverse eects in only 3 (6.8%) pts. All side
eects, which did not exceed CTCAE grade 2, quickly resolved aer ces-
sation of SCSC. 24 pts (54.5%) experienced complete (DS 0) and 8 pts
(18.2%) had incomplete hair preservation (DS 1-2). ree pts had DS 3
(6.8%), and further 9 pts (20.5%) had DS 4. us, the overall success rate
of SCSC was 72.7%.
Conclusions: SCSC is safe and active in order to prevent CIA in pts with
female tract malignancies. Our results are particularly impressive, since
this study represent a more intensively pretreated population as enclosed
in most breast cancer studies.
Disclosure Statement: All authors declare that no conicts of interest have to be
claimed.
623
Feasibility and Satisfaction of Young Cancer Survivors
Participating in Preventive Interventions. A Subgroup
Analysis of the Care for CAYA Program (CFCP)
Simon Elmers 1; Antonia Beitzen-Heineke 1; Julia von Grundherr 1;
Wiebke Jensen 1; Barbara Koch 1; Julia Mann 1; Jannike Salchow 1;
Marianne Sinn 1; Lesley-Ann Straub 1; Luisa Wegert 1; Eik Vettorazzi 2;
Corinna Bergelt 3; Sarah Dwinger 3; Tineke Boesten 4; Gabriele Escherich 4;
Stefan Rutkowski 4; Carl Friedrich Classen 5; Charlotte Niemeyer 6;
Dirk Reinhardt 7; Jörg Faber 8; Gabriele Calaminus 9; Hermann Faller 10;
Peter U. Heuschmann 10; Jens Habermann 11; Inken Hilgendorf 12;
Markus Metzler 13; Michael Köhler 14; Petra Duhm-Harbeck 15;
Claudia Rossig 16; Stefan Bielack 17; Annette Sander 18; Sonja Schuster 13;
Thorsten Langer 15; Uta Dirksen 19; Judith Gebauer 15; Carsten Bokemeyer 1;
Alexander Stein 1
1Universitätsklinikum Hamburg-Eppendorf, Universitäres Cancer Center,
Hamburg, Deutschland
2Universitätsklinikum Hamburg-Eppendorf, Institut für Medizinische Biometrie
und Epidemiologie, Hamburg, Deutschland
3Universitätsklinikum Hamburg-Eppendorf, Institut und Poliklinik für
Medizinische Psychologie, Hamburg, Deutschland
4Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische
Hämatologie und Onkologie, Hamburg, Deutschland
5Universitätsklinikum Rostock, Rostock, Deutschland
6Universitätsklinik Freiburg, Freiburg im Breisgau, Deutschland
7Universitätsklinikum Essen, Essen, Deutschland
8Universitätsklinik Mainz, Mainz, Deutschland
9Universitätsklinikum Bonn, Bonn, Deutschland
10Uni Würzburg, Würzburg, Deutschland
11Universität zu Lübeck, Lübeck, Deutschland
12Universitätsklinikum Jena, Jena, Deutschland
13Universitätsklinikum Erlangen, Erlangen, Deutschland
14Universitätsklinikum Magdeburg, Magdeburg, Deutschland
15Universitätsklinikum Schleswig-Holstein, Schleswig-Holstein, Deutschland
16Universitätsklinikum Münster, Münster, Deutschland
17Klinikum Stuttgart – Olgahospital/Frauenklinik, Stuttgart, Deutschland
18Medizinische Hochschule Hannover, Hannover, Deutschland
19Universitätsklinikum Essen, Essen, Deutschland
Purpose: Children, Adolescents and Young Adult Cancer Survivors
(CAYA) are at in- creased risk for treatment- or disease-related late and
long-term sequelae. Follow up of large cohorts provided associations be-
tween e.g. physical activity and cardiovascular morbidity. Despite these
data, the feasibility, adherence and ecacy of specic interventions e.g. for
lifestyle modication in this patient group is unclear.
Methods: e CfC-P comprehensively assesses potential future problems
and oers dedicated preventive interventions in nutritional behavior,
physical activity and psycho-oncology (ve individual coaching sessions).
CfC-P runs in 14 centers in Germany and is supported by a research
grant from the Federal Joint Committee. Overall 1500 CAYA survivors
are planned to be included. Measures include questionnaires at baseline
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2018
(T1) and follow-ups aer 16 (T2) and 52 weeks (T3). e patient reported
outcome measures for satisfaction was derived from the ZUF-8 question-
naire. is preliminary analysis provides patient reported data at T2 for
the subgroup of patients in Hamburg.
Results: So far about 500 survivors have been recruited in the CfC-P
since 12/2017. 127 CAYAs (57.5% female (n = 73)) of all cancer entities
(28.2% lymphoma, 26.6% carcinoma, 21.8% leukemia, 12.9% sarcoma,
10.5% other) from Hamburg were included in this analysis. Mean age was
25.9 ± 6.3 years. About half of the included patients (59 of 127) already
completed the T2-questionnaire. ZUF-8 questionnaire imply that 90.8%
of all participants rate the intervention with a high or excellent quality and
90.6% are mostly satised or satised with the program. Updated data on
satisfaction and adherence will be presented at the meeting.
Conclusions: e interventions within the CfC-P are feasible and partici-
pants report a high degree of satisfaction. Further analyses are required to
conrm these preliminary results.
650
Health Problems and Quality of Life of Young Cancer Survivors
in the Comprehensive Care for CAYA Program
Simon Elmers 1; Antonia Beitzen-Heineke 1; Julia von Grundherr 1;
Wiebke Jensen 1; Barbara Koch 1; Julia Mann 1; Jannike Salchow 1;
Marianne Sinn 1; Lesley-Ann Straub 1; Luisa Wegert 1; Eik Vettorazzi 2;
Corinna Bergelt 3; Sarah Dwinger 3; Tineke Boesten 4; Gabriele Escherich 4;
Stefan Rutkowski 4; Carl Friedrich Classen 5; Charlotte Niemeyer 6;
Dirk Reinhardt 7; Jörg Faber 8; Gabriele Calaminus 9; Hermann Faller 10;
Peter U. Heuschmann 10; Jens Habermann 11; Inken Hilgendorf 12;
Markus Metzler 13; Michael Köhler 14; Petra Duhm-Harbeck 15;
Claudia Rossig 16; Stefan Bielack 17; Annette Sander 18; Sonja Schuster 13;
Thorsten Langer 15; Uta Dirksen 19; Judith Gebauer 15; Carsten Bokemeyer 1;
Alexander Stein 1
1Universitätsklinikum Hamburg-Eppendorf, Universitäres Cancer Center,
Hamburg, Deutschland
2Universitätsklinikum Hamburg-Eppendorf, Institut für Medizinische Biometrie
und Epidemiologie, Hamburg, Deutschland
3Universitätsklinikum Hamburg-Eppendorf, Institut und Poliklinik für
Medizinische Psychologie, Hamburg, Deutschland
4Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische
Hämatologie und Onkologie, Hamburg, Deutschland
5Universitätsklinikum Rostock, Rostock, Deutschland
6Universitätsklinik Freiburg, Freiburg im Breisgau, Deutschland,
7Universitätsklinikum Essen, Essen, Deutschland
8Universitätsklinik Mainz, Mainz, Deutschland
9Universitätsklinikum Bonn, Bonn, Deutschland
10Uni Würzburg, Würzburg, Deutschland
11Universität zu Lübeck, Lübeck, Deutschland
12Universitätsklinikum Jena, Jena, Deutschland
13Universitätsklinikum Erlangen, Erlangen, Deutschland
14Universitätsklinikum Magdeburg, Magdeburg, Deutschland,
15Universitätsklinikum Schleswig-Holstein, Schleswig-Holstein, Deutschland
16Universitätsklinikum Münster, Münster, Deutschland
17Klinikum Stuttgart – Olgahospital/Frauenklinik, Stuttgart, Deutschland
18Medizinische Hochschule Hannover, Hannover, Deutschland
19Universitätsklinikum Essen, Essen, Deutschland
Purpose: Children, Adolescents and Young Adults Cancer Survivors
(CAYA) are at in- creased risk for treatment- or disease-related late and
long-term sequelae. Assessing the individual health problems, quality of
life and unmet needs in regular intervals and determin- ing potential pre-
ventive interventions is of utmost importance to improve long-term out-
comes in this particular vulnerable population.
Methods: e Federal Joint Committee funded CfC-P comprehensively
assesses potential future problems and oers need based preventive inter-
ventions (nutritional behavior, physi- cal activity and psycho-oncology).
Comprehensive questionnaires compiled of dierent vali- dated question-
naires are conducted every 12 months in the CfC-P. e patient reported
out- come measures for health was the EQ5D-L questionnaire, for self
reported health problems the NCCN Distress ermometer and Problem
List, for need for support the SCNS-TF-9, and for quality of life (QoL) the
EORTC QLQ-C30. is preliminary analysis provides patient re- ported
data for the subgroup of patients in Hamburg and Lübeck at T1.
Results: 172 CAYAs (59.9% female (n = 103); n = 127 in Hamburg, n =
45 in Lübeck) from the CfC-P were included in this analysis. ey are of
all cancer entities (29.6% lymphoma, 21.9% carcinoma, 21.9% leukemia,
12.4% sarcoma, 14.2% other). Mean age was 25.7 ± 6.9 years. All partici-
pants completed T1-questionnaire. 21.5% reported not or slight problems
regarding anxiety and depression, 20.9% reported no or slight pain or dis-
comfort, 15.8% reported no or slight problems in usual activities, 8.2%
reported no or slight mobility problems, 1.3% reported no or slight prob-
lems in self-care. e mean health status (EQ5-D- VAS) was 75.91 out of
100 (SD = 18.9). e most important health problems were worries (60%),
fatigue (50.3%), pain (48.1%), fears (42.6%) and sleep (42.3%). Further
data will be presented at the congress.
Conclusions: CAYAs have a large variety of health problems, unmet needs
and QoL issues.
730
Sceletal Muscle Hypertrophy in Cancer Patients and Survivors:
A Meta Analysis
Maximilian Köppel 1; Katlynn Mathis 2; Kathryn Schmitz 2;
Joachim Wiskemann 1
1AG: Onkologische Sport- und Bewegungstherapie, Medizinische Onkologie ,
Nationales Centrum für Tumorerkrankungen, Heidelberg, Deutschland
2Hershey Medical Center, Pennsylvania State University, Hershey, United States
Purpose: Depending on cancer site 14 to 80% of patients show signicant
loss of muscle mass (Sarcopenia), caused by physiological factors associat-
ed with the disease, its therapy and lifestyle changes1. Sarcopenia is known
to have a negative impact on treatment toxicity, the patients’ physical
function1 and their prognosis2. A promising approach to prevent this loss
of muscle mass is the utilization of resistance training. A meta-analysis
was conducted to verify this eect.
Methods: A systematic literature search was conducted in Pubmed, Co-
chrane Library, SportDiscus and CINAHL. Randomized controlled exer-
cise trials where eligible if lean body mass or muscle mass were assessed.
Primary outcome was post-test muscle mass. e model was adjusted for
baseline group dierences. Additionally, impact of supervision, therapy
status, and training parameters were investigated. Model t was evaluated
via several information criteria.
Results: We included 31 studies into the primary analysis. Participants of
the intervention group
showed a pooled increase in muscle mass of 0.83 kg (95%CI: 0.26, 1.39)
compared to their controls. e eect was even larger when only super-
vised interventions were anaylsed (pooled mass increase of 1.20kg (0.17,
2.23)). Aer adjusting for supervision the main eect was almost van-
ished (0.25; 95%CI: -0,43, 0.92). Other predictors were lacked explanatory
power.
Conclusions: Resistance training can help cancer patients and survivors
to ght sarcopenia. However, analysis revealed that interventions need to
be supervised in order to gain signicant eects on muscle mass.
References:
1. Morishita S. Prevalence of sarcopenia in cancer patients: review and future
directions. Int J Phys Med Rehabil. 2016;4.
2. Reisinger KW, Bosmans JWAM, Uittenbogaart M, et al.: Loss of skeletal muscle
mass during neoadjuvant chemoradiotherapy predicts postoperative mortality
in esophageal cancer surgery. Annals of surgical oncology. 2015;22:4445-52.
Disclosure Statement: e authors have no conicts of interest that relate to this
abstract.
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2018
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2018
732
Safety and Feasibility of Paravertebral Muscle Training
in Patients with Unstable Spinal Metastases Undergoing
Palliative Radiotherapy
Friederike Rosenberger 1; Tanja Sprave 2, 3; Harald Rief 4;
Joachim Wiskemann 1
1AG Onkologische Sport- und Bewegungstherapie, Abteilung Medizinische
Onkologie, Nationales Centrum für Tumorerkrankungen (NCT),
Universitätsklinikum Heidelberg, Heidelberg, Deutschland
2Heidelberger Institut für Radioonkologie (HIRO), Universitätsklinikum
Heidelberg, Heidelberg, Deutschland
3Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg,
Deutschland
4Radioonkologische Praxis Bad Godesberg, Bonn, Deutschland
Purpose: Cancer patients with unstable spinal metastases have so far been
excluded from exercise due to fear of fractures. Because a previous study
in patients with stable spinal metastases found positive training eects (1),
safety and feasibility of paravertebral muscle training was investigated in
patients with unstable spinal metastases in an exploratory RCT (2).
Methods: Sixty cancer patients with spinal metastases (Taneichi score ≥D)
scheduled for radiotherapy were randomized to an intervention group
(INT, n=27 starters) or a control group (CON, n=29 starters). INT un-
derwent isometric paravertebral muscle training daily during 10±2 days
of radiotherapy and continued home-based on 3 days/week for 3 months.
CON received muscle relaxation. Adverse events and adherence (primary
endpoints), strength, pain and QoL (secondary endpoints) were assessed.
Results: ere were no training-related adverse events. During radiother-
apy, 67% of patients in INT and 55% of patients in CON attended ≥80%
of the planned training sessions. Plank position holding time (strength)
increased by 24±28 s in INT and dropped by 2±34 s in CON by the end of
radiotherapy (p=0.01). During home-based training, 64% of patients per-
formed ≥80% of the planned training sessions. ere were no dierences
between groups for pain or QoL (p>0.05).
Conclusions: Isometric training of the paravertebral muscles is safe and
in about 2/3 of cancer patients with unstable spinal metastases feasible.
Now, larger studies powered for clinical endpoints should be conducted
and the training program can be recommended to patients interested in
physical training.
References:
1. Rief H et al. e eect of resistance training during radiotherapy on spinal
bone metastases in cancer patients - A randomized trial. Radiother Oncol.
2014;112(1):133-139
2. Rosenberger F et al. Kräigungsgymnastik für die paravertebrale Muskulatur
bei Patienten mit instabilen Wirbelsäulenmetastasen begleitend zur palliativen
Radiotherapie. 1. Deutscher KrebsForschungsKongress 2018
Disclosure Statement: No conict of interest.
793
Treating CIPN with Complementary Nursing Procedures –
Recommendations Developed with a Process of Consensus
Finding and a Systematic Literature Review
Nadja Klafke 1; Regina Stolz 2; Petra Neuberger 3; Ute Heyder 4;
Monika Layer 5; Marcela Winkler 6; Christel Idler 6; Elke Kaschdailewitsch 7;
Rolf Heine 8; Heike John 9; Tatjana Zielke 9; Beeke Schmeling 9;
Sosamma Joy 10; Isabel Mertens 10; Claudia Witt 11; Diana Steinmann 9;
Petra Voiß 10
1Abteilung Allgemeinmedizin und Versorgungsforschung, Universitätsklinikum
Heidelberg, Heidelberg, Deutschland
2Institut für Allgemeinmedizin und Interprofessionelle Versorgung,
Universitätsklinikum Tübingen, Tübingen, Deutschland
3Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg,
Deutschland
4Frauenklinik, Städtisches Klinikum Karlsruhe, Karlsruhe, Deutschland
5Zentrum für Integrative Medizin, Kantonsspital St. Gallen, St. Gallen, Schweiz
6Naturheilkunde und Integrative Medizin, Robert-Bosch-Krankenhaus,
Stuttgart, Deutschland
7Zentrum für Integrative Onkologie, Die Filderklinik, Filderstadt-Bonlanden,
Deutschland
8Netzwerk anthroposophische Pege in Deutschland, Akademie für
Pegeberufe an der Filderklinik, Die Filderklinik, Filderstadt-Bonlanden,
Deutschland
9Klinik für Strahlentherapie und Spezielle Onkologie, Medizinische Hochschule
Hannover, Hannover, Deutschland
10Klinik für Integrative Onkologie / Naturheilkunde, Kliniken Essen-Mitte, Essen,
Deutschland
11Institut für komplementäre und Integrative Medizin, Universitäts Spital Zürich,
Zürich, Schweiz
Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a
common symptom in cancer patients with prevalence rates ranging up to
85%. Symptom management strategies are highly relevant, because CIPN
inuences patients’ quality of life, and prevails even aer completion of
primary treatment. e aim of the current project was to make recom-
mendations for preventing or treating CIPN with non-pharmacological
complementary nursing treatments.
Methods: e mixed methods approach included, rst, a structured ex-
pert consensus process (workshop and further written rounds) for dis-
cussing and presenting nursing applications for CIPN. Each application
was evaluated regarding 5 essential domains: safety, clinical expertise,
eort of training, practical feasibility, research evidence. en a system-
atic literature review was conducted within the databases MEDLINE,
Cochrane Central, CINAHL, PsycINFO, and PEDro.
Results: e expert panel consisted of 16 participants with a naturopathic
background with experience in cancer treatment and care, representing 6
dierent institutions. In total, 6 interventions were discussed and agreed
upon, i.a., axseed bath or tactile stimulation strategies (e.g., beeswax dis-
persing, rap bath), for preventing CIPN. Overall 14 interventions were
discussed and consented for treating CIPN, i.a., embrocations with Aconit
or Arnica oil. All interventions were judged as safe and very feasible in
daily patient care. e extent of the clinical expertise has been consented
by evaluating the perceived eect of the mean of all treated patients, rep-
resented on a scale from 0=no eect until 5=maximum eect. In total, 9
interventions have been consented as ≥3. e literature review conrmed
the eects only for a few of these interventions, as the research evidence is
rather scarce in this supportive care area.
Conclusions: Complementary nursing applications might have the po-
tential to prevent or treat CIPN in patients aected by cancer. More re-
search, clarication, and education in this eld is highly warranted.
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2018
Index
2018
798
Social Service Counseling in German Breast Cancer Centers:
What does Account for Dierences in the Utilization?
Clara Breidenbach 1; Simone Wesselmann 1; Nora Tabea Sibert 1;
Sebastian Dieng 2; Christoph Kowalski 1 and the German Breast Cancer
Centres Participating in the Oncobox Research Project 3
1Deutsche Krebsgesellschaft e. V., Berlin, Deutschland
2OnkoZert GmbH, Neu-Ulm, Deutschland
Purpose: Cancer patients oen face enormous economic and social chal-
lenges. For this reason, it is compulsory for cancer centers certied by the
German Cancer Society to oer social service counseling (SSC) to every
patient. It turns out, however, that the utilization of SSC varies between
breast cancer centers. is analysis addresses the question to what extent
SSC rates vary across German breast cancer centers and whether patient
characteristics account for these dierences.
Methods: A multilevel analysis has been performed including 16,217
breast cancer patients nested in 13 German certied breast cancer centers.
Data were collected within the project “OncoBox Research” between 2014
and 2019. Data analysis was performed with STATA 15.
Results: e intra-class correlation (ICC) for the null model (ICC=0.31)
indicates that 31% of the utilization of SSC depends on the center. Patients
older than 84 years use SSC signicantly to a lesser degree than patients in
the reference group (45-64 years), patients between 25- and 44-years old
use SSC marginally to a lesser degree than patients in the reference group;
no signicant eects were found for other age groups. Metastasized pa-
tients use SSC to a higher extent than patients without metastases. Patients
receiving surgery with a recommendation for chemotherapy utilize SSC to
a higher degree than patients receiving surgery without recommendation
for chemotherapy (reference group). Patients that did not undergo sur-
gery utilize SSC to a lesser degree than patients receiving surgery without
recommendation for chemotherapy. SSC utilization is higher the later the
patients were diagnosed between 2014 and 2019.
Conclusions: e analysis conrms that utilization of SSC varies be-
tween breast cancer centers. Disease severity is associated with higher use
of SSC. Above, age and therapy type are predictors for SSC utilization.
Further subgroup analyses regarding therapy types will be available at the
congress. Cohort eects indicate a better adaption of certication require-
ments over time in the centers.
845
Demand for Integrative Medicine Among Women with Breast
and Gynecological Cancer - A Multicenter Cross-Sectional
Study in South and North Germany
Donata Grimm 1; Soa Mathes 2; Alexander Hapfelmaeier 3;
Barbara Schmalfeldt 4; Volkmar Müller 4; Marion Kiechle 2; Evelyn Klein 2;
Anna Jaeger 4; Achim Rody 5; Daniela Paepke 2
1Department of Gynecology and Obstetrics, University Medical Center
Schleswig-Holstein, Campus Lübeck , Deutschland
2Department of Gynecology and Obstetrics, Klinikum rechts der Isar, TU Munich,
Munich, Deutschland
3Institute of Medical Informatics, Statistics and Epidemiology, Klinikum rechts
der Isar, TU Munich, Munich, Deutschland
4Department of Gynecology and Gynecologic Oncology, University Medical
Center Hamburg-Eppendorf, Hamburg, Deutschland
5Department of Gynecology and Obstetrics, University Medical Center
Schleswig-Holstein, Campus-Lübeck, Lübeck, Deutschland
Purpose: e aim of this multicenter cross-sectional study is to analyze a
cohort of breast cancer (BC) and gynecological cancer (GC) patients with
regard to their interest in, perspectives on and demand for integrative
therapeutic health approaches including integrative therapies.
Methods: Cancer patients with the diagnosis of BC or any other GC were
surveyed at their rst attendance of a specialized integrative outpatient
clinic at two university medical centers in Germany. Data were collected
through a validated standardized questionnaire. Treatment goals regard-
ing integrative medicine (IM) were evaluated and dierences between
BC- and Ovarian cancer (OC) patients were elucidated.
Results: A total of 340 patients entered into the study. In total, 95.3% pa-
tients claimed to be interested in IM. Interest in IM correlated with older
age, recent chemotherapy, higher education and advanced disease at time
of enrolment without reaching statistical signicance. A total of 89.8% in
the BCG and 88.9.1% in the OCG used any integrative method at time of
enrolment. e methods mostly used were exercise therapy and vitamin
supplementation. e major short-term goal of the BCG was reduction of
side eects of the conventional therapy, the major long-term goal slowing
of tumor progression. In the OCG major short- and long-term goals were
slowing tumor progression and prolonging survival time. When analyz-
ing side eects, patients in the OCG are more impaired than those in the
BCG, reaching statistical signicance in the category pain (p=0.001), ob-
stipation (<0.001), and depressive symptoms (p=0.005).
Conclusions: Our data demonstrates a high overall interest and frequent
use of IM in BC and OC patients. is supports a strong demand of both
patient groups for specialized counseling in IM and implementation of
integrative treatments concomitant to conventional oncological treatment
regimes. Primary tumor site, cancer diagnosis and side eects have a rele-
vant impact on patients` perception and opinions about IM.
Disclosure Statement: No conict of interest.
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Index
2018
Surgical Oncology
Poster
25
Resection of the Primary Tumors Prolonged the Overall and
Progression Free Survival in Patients with Neuroendocrine
Neoplasms Stage IV Treated by Peptide Radionuclide Therapy
(PRRT)
Daniel Kämmerer 1; Matthias Twrznik 1; Harshad R. Kulkrani 2;
Dieter Hörsch 3; Susanne Sehner 4; Richard Baum 2; Merten Hommann 1
1Klinik für Allgemeine Chirurgie / Viszeralchirurgie, Zentralklinik Bad Berka
Bad Berka , Deutschland
2Klinik für Molekulare Radiotherapie, Zentralklinik Bad Berka, Bad Berka,
Deutschland
3Klinik für Innere Medizin, Gastroenterologie und Endokrinologie, Zentralklinik
Bad Berka, Bad Berka, Deutschland
4Institut für medizinische Biometrie und Epidemiologie, Universitätsklinikum
Hamburg-Eppendorf (UKE), Hamburg, Deutschland
Purpose: To evaluate the benet of a primary tumor (PT) resection aer
a treatment with peptide radionuclide therapy (PRRT) in patients with a
metastasized neuroendocrine neoplasms stage IV.
Methods: Retrospectivly, we analyzed prospective data of 889 patients
with advanced NEN (G1-3) in stage IV treated with PRRT (at least 1 cy-
cle). PT was removed in 486 / 889 patients (group 1) and group 2 enfolded
403 / 889 patients without a PT resection before PRRT. Progression-free
survival (PFS) and overall-survival (OS) was determined by 68Ga-SSTR-
PET/CT applying RECIST and EORTC.
Results: e majority of patients had their primary in pancreas (n = 335)
and small intestine (n = 284). Group 1 and 2 were treated with a mean of 4
cycles of PRRT (p = 0.835) with a mean cumulative radioactivity of 21.6 ±
11.7 and 22.2 ± 11.2 GBq (p = 0.407). Median OS was 134.0 (CI: 118 – 147
group 1) vs. 67.0 months (CI: 60 – 80 group 2; HR 2.79; p < 0.001). Median
PFS was 18.0 (CI: 15 – 20 group 1) vs. 14.0 months (CI: 15 – 18 group 2;
HR 1.21; p = 0.012).
Conclusions: Prior to PRRT PT resection in pancreatic and small in-
testine neuroendocrine neoplasms stage IV resulted in a prolonged PFS
and OS.
Reference:
1. Kaemmerer D. et al. Ann Surg 2019
Disclosure Statement: Kaemmerer received travel support by the companies
Ipsen, Pzer, Novartis. Lecture fee: company Ipsen.
58
Laparoscopic Salvage Resection for Patients with Disease
Progression After Transarterial Chemoembolization: A New
Treatment Algorithm in Primary Liver Cancer?
Emrullah Birgin; Christoph Reissfelder; Nuh N. Rahbari
Universitätsmedizin Mannheim, Chirurgische Klinik, Mannheim, Deutschland
Purpose: Primary liver cancer patients with disease progression aer
transarterial chemoemboliztion (TACE) have traditionally been consid-
ered candidates for palliative systemic treatment or best supportive care
only. We herein report a clinical series of patients with progressive disease
following TACE who underwent minimally-invasive salvage hepatic re-
section (HR) based on multidisciplinary board decision.
Methods: A retrospective review of patients who underwent salvage HR
following non-responding TACE between 2018 and 2019 was performed.
Clinicopathological outcomes were collected and presented as medians
and ranges.
Results: A total of seven patients (ve males, two females) received a me-
dian of 4 (1-5) TACE treatments with a median dose of 55mg (15-90mg)
epirubicin. Laparoscopic HR was performed at a median of 55 days
(14-147 days) aer the last TACE session. Conversion to a mini laparoto-
my was required in 1 patient. Apart from a supercial surgical site infec-
tion in 1 patient no further postoperative complications were observed.
Histopathological examination revealed cholangiocarcinoma (CCC) on
nal diagnosis in 2 patients. e R0 resection rate was 86%. Median post-
operative length of hospital stay was 5 days (4-12 days). Aer a median
follow-up of 60 days (14-125 days) no patient had recurrent disease.
Conclusions: Laparoscopic HR is safe and enables salvage treatment in
patients with primary liver tumors and disease progression aer TACE.
Further studies are needed to evaluate the long-term outcomes of this
novel treatment approach.
Reference:
1. Lei et al, Response to transarterial chemoembolization as a selection criterion
for resection of hepatocellular carcinomas, Br J Surg 2016 Jun;103(7):881-90
Disclosure Statement: None of the authors have any conicts or nancial support
to disclose.
389
Altered Diversity and Composition of the Microbiome in
Patients with Primary Untreated Colorectal Cancer
Melanie Langheinrich 1; Stefan Wirtz 2; Klaus Weber 1; Robert Grützmann 1;
Stephan Kersting 1
1Universitätsklinikum Erlangen, Klinik für Allgemein- und Viszeralchirurgie,
Erlangen
2Universitätsklinikum Erlangen, Forschungsabteilung Medizinische Klinik 1,
Erlangen
Purpose: Recently, the gut microbiome has been associated with tumor
development and progression and several authors have tried to link cer-
tain bacterial species to the colorectal cancer. e aim of the EMA-CRC
study (Erlanger microbiome analysis colorectal cancer) is to characterize
the microbiome prole of matched stool, tumor and mucosa samples from
the proximal and distal resection margin. Furthermore we want to assess
the eect of surgery and neoadjuvant therapy (e.g. chemo/ radiochemo-
therapy) on the gut microbiome.
Methods: Since 12/2018 we included 80 patients with previously untreat-
ed CRC in the study. Microbiota proles were characterized by amplica-
tion of the V3/V4 region of the 16SrRNA gene and deep sequencing using
the Illumina MiSeq platform. Stool samples were collected preoperatively,
or prior to the beginning of neoadjuvant therapy, 4 weeks aer ending
of neoadjuvant therapy and postoperative. Intraoperatively, tumor tissue
samples and mucosa samples from healthy regions were obtained.
Results: To date (study still recruiting), 67 stool samples were analysed.
For colon cancer alpha and beta diversity of the stool samples were sig-
nicantly dierent compared preoperative versus postoperative (for rectal
cancer similar results were observed). Compared with preoperative sam-
ples, the postoperatively collected samples exhibited a signicant increase
of potentially pathogenic bacteria such as Escherichia Shigella, Veillonel-
la, Clostridia and interestingly Fusobacterium. e butyrate producing
bacteria Alistipes was identied in the preoperative stool samples.
Conclusions: Surgery exert an eect on the gut microbiome of CRC
patients. Due to the potentially modiable nature of gut bacteria a better
understanding of the microbiome in colorectal cancer may lead to a
microbiota based intervention (e.g. probiotics, prebiotics or antibiotics)
during pre/postoperative management.
Disclosure Statement: No disclosures.
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Index
2018
403
Early Onset Colorectal Liver Metastases – The More Aggressive
Disease?
Katharina Joechle; Magdalena Menzel; Stephan Herrmann;
Stefan Fichtner-Feigl; Sven A. Lang
Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie,
Freiburg, Deutschland
Purpose: Patients with early onset colorectal cancer (CRC) are well known
to show dierent demographic, pathologic and clinical patterns compared
to patients with late onset disease (LOD) 1, 2. However, colorectal liver
metastases (CRLM) of patients with early onset disease (EOD) are not
well examined.
Methods: Patients who underwent resection for colorectal liver metas-
tases at the University Medical Center between 2015 and 2018 were in-
cluded and evaluated regarding short and long term outcome. Patients
who were diagnosed with CRC at the age of 45 or younger were dened
as early onset.
Results: In total, 194 patients could be identied with EOD being present
in 21 patients (11%). Patients with EOD were more oen female com-
pared to patients with LOD (p=0.005). While histopathologic features and
mutation status (KRAS, BRAF, MSI) were comparable between the two
groups, there was a trend for a more aggressive surgical strategy in pa-
tients with EOD (simultaneous resection of extrahepatic disease/HIPEC
p=0.058; ALPPS procedure p=0.098). Although the proportion of patients
who received systemic treatment (neoadjuvant p=0.703; adjuvant=0.919)
was similar between the groups, EGF-R antibodies combined with neoad-
juvant chemotherapy were more commonly used in the group of patients
with EOD (p=0.05). Recurrence-free survival (RFS; p=0.611), liver-spe-
cic RFS and overall survival did not dier between patients with EOD
and LOD.
Conclusions: Although patients with EOD may require a more aggressive
surgical and oncological treatment, survival was comparable between pa-
tients with EOD and LOD.
References:
1. Yeo H, Betel D, Abelson JS, Zheng XE, Yantiss R, Shah MA. Early-onset Colo-
rectal Cancer is Distinct From Traditional Colorectal Cancer. Clin Colorectal
Cancer. 2017 Dec;16(5)293-299.
2. Murphy CC, Lund JL, Sandler RS. Young-Onset Colorectal Cancer:
Earlier Diagnoses or Increasing Disease Burden? Gastroenterology.2017
Jun;152(8):1809-1812.
Disclosure Statement: None of the authors have anything to disclose.
538
AssociatedLiverPartitionandPortalVein Ligation for
Staged Hepatectomy (ALPPS)for Cholangiocarcinoma. Is the
Risk Worth Taking? Single Centre Experience with 21 Right
Trisectionectomies and Long Term Oncological Results
Ivan Capobianco; Jens Rolinger; Alfred Königsrainer; Silvio Nadalin
Universitätsklinikum Tübingen, Klinik für Allgemeine, Viszeral- und
Transplantationschirurgie, Tübingen, Deutschland
Purpose: Bile duct cancer (CCA) remains a major challenge among liver
tumors and surgery remains the only curative option, whereas a radical
resection is possible, with a 1, 3 and 5 years-survival for iCCA of 80-86%,
50-60% and 15-40% and for phCCA of 70-80%, 27-42% and 13-40%.
ALPPS could expand the rection possibilities also in patients with a small
future liver remant. However, due to the high morbidity and mortality
CCA is oen considered a relative contraindication to ALPPS. e pur-
pose of this study is to analyze the long-term outcome of patients that
underwent ALPPS for cholangiocarcinoma.
Methods: We retrospectively analyzed our single center experience on
the use of ALPPS for Cholangiocarcinoma focusing on postoperative out-
come, patient survival and tumor recurrence.
Results: Between November 2010 and January 2019 we performed 53
ALPPS, of them 21 ALPPS for suspected cholangiocarcinoma (10 perihi-
lar (phCCA) and 11 intrahepatic (iCCA)) with a feasibility of 100%. Me-
dian age was 70,3 and 68,3 years, respectively. BDA was performed in all
phCCA and 8 iCCA. A R0 status was reached in 15 patients (6 phCCA,
9 iCCA). Severe Morbidity (≥IIIb according Dindo-Clavien) was 60% for
phCCA and 45% for iCCA. e postoperative mortality rate was 20% for
phCCA and 18% for iCCA. Overall mortality aer recurrence was ob-
served in 1 patient with phCCA (12,5%) and 4 patients with iCCA (44%).
A tumor recurrence was observed in 1 patient with phCCA (12,5%) and
7 patients with iCCA (78%). Median disease free survival time was 29,5
months for the phCCA and 3,9 months (1-20,5) for iCCA. 1-, 3- and
5- year cumulative survival were respectively 80%, 80% and 60% for
phCCA, 64%, 53% and 40% for iCCA.
Conclusions: Despite a high morbidity, with a precise patient selection
mortality can be avoided and ALPPS can be used for cholangiocarcinoma,
particularly in phCCA, to expand the pool of resectable patients, that oth-
erwise have no therapeutical possibility and poor outcome.
Disclosure Statement: I have nothing to disclose.
611
Robotic-Assisted Resection of Primary Hepatic Tumours and
Hepatic Metastasis Using Isocyanine Green
Anne-Sophie Mehdorn; Jan Niclas Kersebaum; Jan Henrik Beckmann;
Jan-Hendrik Egberts; Thomas Becker
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Allgemeine,
Viszeral-, Transplantations-, Thorax- und Kinderchirurgie, Kiel, Deutschland
Purpose: Isocyanine green (ICG) is a uorescent dye, which accumulates
in degenerated hepatic cells. ICG-accumulation becomes visible using
near infrared light and may help to dierentiate degenerated from normal
tissue. is study aimed to test the feasibility of preoperative iv-ICG-ap-
plication for dierent types of tumours and real-time visualisation during
robotic assisted primary and metastatic liver resections.
Methods: Patients who were planned for a robotic assisted resection of
hepatic tumours or metastasis received 25 mg iv-ICG (Diagnostic Green
GmbH, Germany) the evening before surgery. All procedures were per-
formed using the DaVinci®-Xi robotic system with the included near in-
frared light FireFlyTM®.
Results: Between February and August 2019, 13 consecutive patients
were included. Nine patients presented with hepatic metastases of mam-
ma, colon, choroid coat and esophageal carcinomas. ICG-accumulation
helped to locate metastases more precisely and perform tissue sparing re-
sections usingDaVinci®-Xi in most cases. Interestingly, ICG accumulated
in the metastasis of an esophageal carcinoma which was hence resected.
Interestingly, there was no vital tumour tissue in the pathological analysis.
Metastases of a choroid coat melanoma only showed ICG-accumulation
halo-like at the outer rim of the metastases. Four patients had primary
hepatic tumours. In patients suering from liver cirrhosis, ICG accumu-
lated ubiquitously in the cirrhotic tissue and did not help to dierentiate
tumour from normal liver tissue.
Conclusions: Preoperative iv-ICG-application can help to perform
DaVinci®-assisted resection of primary and metastatic hepatic lesions.
However, the performing surgeon should not only rely on non-quantitative
ICG-colouring as cirrhotic tissue and other entities showed too much
ICG-uptake. Preoperative imaging and intraoperative ultrasound are
still mandatory for pre- and intraoperative planning. At the moment,
ICG serves as an additional tool. With future improvements of dyes and
devices more tailored approaches may be possible.
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2018
Index
2018
631
Early Onset Colorectal Cancer with Liver Metastases – Low
Incidence of High-Risk Features but Early Recurrence
Katharina Joechle; Magdalena Menzel; Stephan Herrmann;
Stefan Fichtner-Feigl; Sven A. Lang
Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie,
Freiburg, Deutschland
Purpose: e incidence of colorectal cancer (CRC) is increasing among
younger patients 1,2. However, little is known about features of colorectal
liver metastases (CRLM) in patients with early onset disease.
Methods: Patients who were diagnosed with colorectal cancer at the age
of 45 or younger and underwent resection of CRLM at the University
Medical Center Freiburg between 2008 and 2018 were included and eval-
uated regarding short and long term outcomes.
Results: Among 578 patients undergoing liver resection for CRLM, 44
(7.6%) were identied with early onset disease. is proportion increased
over time (2008-2011: 5.2%, 2012-2014: 7.1%, 2015-2018: 10.8%). In 89%
CRC was of sporadic origin, only 3 patients were diagnosed with FAP and
1 patient had a chronic inammatory bowel disease. Although high-risk
mutations such as KRAS and BRAF occurred in only 25% and 5% and
none of the patients had a microsatellite instable tumor, RFS was poor
(3-year RFS: 18.4%) with only 46% and 43% of patients having been sys-
temically treated with neoadjuvant or adjuvant chemotherapy. Liver-spe-
cic RFS was 29.3% and OS 58.4% aer 3 years.
Conclusions: Despite few high-risk characteristics among patients with
CRLM and early onset disease, RFS is poor. is might favor a more ag-
gressive strategy of systemic treatment in these patients.
References:
1. Bailey CE, Hu C-Y, You YN, Bednarski BK, Rodriguez-Bigas MA, Skibber JM,
et al. Increasing disparities in the age-related incidences of colon and rectal
cancers in the United States, 1975-2010. JAMA Surg. 2015;150:17–22.
2. Austin H, Henley SJ, King J, Richardson LC, Eheman C. Changes in colorectal
cancer incidence rates in young and older adults in the United States: what
does it tell us about screening. Cancer Causes Control. 2014;25:191–201
Disclosure Statement: None of the authors have anything to disclose.
708
Long-Term Local Tumor Control of Kypho-IORT Treated Spinal
Metastases
Frederic Bludau 1; Laura Winter 2; Udo Obertacke 1; Grit Welzel 2;
Frank Giordano 2
1Universitätsklinik Mannheim, Orthopädisch-Unfallchirurgisches Zentrum,
Mannheim, Deutschland
2Universitätsklinik Mannheim, Klinik für Radio-Onkologie, Mannheim,
Deutschland
Purpose: e Kypho-IORT is an established method for local therapy of
vertebral metastases consisting of local irradiation and cement augmenta-
tion and stabilization of the vertebral body. e technical and procedural
safety [1] and in a phase 1/2 study the medium-term local tumor control
has been demonstrated [2]. e long-term tumor control is unclear so far.
Methods: A single-center Kypho-IORT-collective were contacted and an
interview-follow-up was carried out. e last medical imaging (CT and/or
MRI) were evaluated. External follow-up imaging was acquired. A long-
term follow-up could be created.
is is a retrospective, non-comparative cohort study.
Results: A complete data set was obtained in 100/104 treated patients
(n=27 alive, n=73 deceased). 143 Kypho-IORT procedures were per-
formed in 104 pat. Longest follow-up period was 9 years.
A total of 10 local recurrences (6.9%, n=10/143) occurred; A Kaplan-
Meier calc. was performed. A local relapse-free survival of 93% at 12 m
and of 80% at 5 y. e average overall survival is 2.2 years.
Entities consisted of 49% breast, 14% prostate, 15% bronchial, 8% GI
tumors and 15% other.
Conclusions: is study shows the long-term therapeutic eect of Ky-
pho-IORT, comparable data from other centers do not exist.
e excellent medium-term local tumor control in the phase 1/2 study
was conrmed by long-term course. Compared to other interventions
(SBRT), Kypho-IORT appears at least equal [3].
References:
1. Wenz F et al. Kypho-IORT--a novel approach of intraoperative radiotherapy
during kyphoplasty for vertebral metastases. Radiat Oncol. 2010
2. Bludau F et al. Phase I/II trial of combined kyphoplasty and intraoperative
radiotherapy in spinal metastases. Spine J. 2018
3. Husain ZA et al. Stereotactic body radiotherapy for de novo spinal metastases:
systematic review. J Neurosurg Spine 2017
Disclosure Statement: e authors received nancial support for establishing the
method and for teaching the method in specimen courses. Financial travel support
for congresses was given.
715
Measuring the Integration of Radiotherapy Plus Surgery for
Resectable Hepatocellular Carcinoma: A Pilot Study from
National Cancer Center of China
Xinyu Bi; Zhiwen Luo
National Cancer Center/National Clinical Research Center for Cancer/Cancer
Hospital, Chinese Academy of Medical Sciences and Peking Union Medical
College, Beijing, China
Purpose: To assess oncologic outcomes and liver reserve condition aer
a combined approach of neoadjuvant radiotherapy followed by surgery.
Methods: A phase 2, single-arm trial, with patient accrual from Septem-
ber 1, 2016, to August 31, 2018 (median follow-up, 16 months), was per-
formed at the national cancer center of China. Patients 18 years or older
with high recurrence risk and good performance status, with adequate
liver reserve to undergo surgical resection, were studied. And patients un-
derwent neoadjuvant radiotherapy (IMRT or VMAT) followed by surgery
no more than 15 weeks later. Main outcomes focused on the recurrence of
HCC and the liver reserve condition.
Results: So far, twenty male patients (mean [SD] age, 55.13 [8.453] age)
were enrolled. 16 patients underwent a combined approach of neoadju-
vant radiotherapy followed by surgery and were evaluable for the primary
end point. e rates of local lesion necrosis, well response, MVInegative aer
radiotherapy are 68.75%, 68.75%, 62.5% respectively. e 30- and 90-day
postoperative mortality rates were both 0%. Surgical complications rate is
12.5%, however without severe complications as well as liver failure. Re-
currence accounts for 18.75% of the patients. And progression free surviv-
al was observed as mean period of 13.5 months (quartile 10-19 months).
Conclusions: e combined approach holds a security for patients with
resectable HCC and there was no perioperative mortality, no inuence of
neoadjuvant radiotherapy on liver reserve. Further studies are needed to
evaluate this combined approach compared with surgical resection alone.
Reference:
1. Siegel R L, Miller K D, Jemal A. Cancer statistics, 2019[J]. CA: A Cancer
Journal for Clinicians, 2019, 69(1):7-34.
Disclosure Statement: is study received supports from the funds: LC2016A07;
Beijing Hope Run Special Fund of Cancer Foundation of China.
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2018
750
Surgical Treatment of Rectal Cancer Patients Aged 80 Years
and Older - A German Nationwide Analysis Comparing Short-
and Long-Term Survival After Laparoscopic and Open Tumor
Resection
Vinzenz Völkel 1, 2; Teresa Draeger 1, 2; Michael Gerken 2;
Monika Klinkhammer-Schalke 2; Alois Fürst 1
1Caritas Krankenhaus St. Josef, Regensburg, Deutschland
2Tumorzentrum Regensburg, Regensburg, Deutschland
Purpose: Minimally invasive removal of rectal tumors has proven to be
a safe alternative to the open approach. Despite increased use of laparos-
copy, its eligibility for patients aged 80 years and older requires further
exploration.
Methods: is study compares perioperative mortality and 5-year overall,
disease-free, and relative survival aer laparoscopic and open surgery in
rectal cancer patients aged 80 years and older. Data derive from 30 German
regional cancer registries covering approximately one quarter of the entire
German population. All primary nonmetastatic rectal adenocarcinoma
cases with surgery between 2005 and 2014 were eligible for inclusion. To
compare survival rates, Kaplan-Meier analysis, a relative survival model,
and multivariable Cox regression were applied; a sensitivity analysis
assessed bias by exclusion.
Results: 1,532 patients were included, of whom 17.1% underwent laparo-
scopic procedures. 30 days aer surgery, 2.7% of the laparoscopy patients
had died compared to 7.0% in the open surgery group. e multivariable
analysis conrmed that minimally invasive procedures are followed by
a lower 30-day postoperative mortality risk (odds ratio, OR, 0.352; 95%
condence interval, CI, 0.161e0.771; p =0.009). With a 5-year disease-free
survival rate of 52.0 vs. 47.6% (p = 0.557), only a nonsignicant long-term
advantage of the minimally invasive approach was observed.
Conclusions: Given the results of this study, older rectal cancer patients
are likely to benet from the laparoscopic approach in the short term,
while there are no disadvantages in terms of long-term survival. ere-
fore, laparoscopy should be considered as standard procedure for patients
aged 80 and older as well.
758
Neoadjuvant Chemotherapy with Gemcitabine Plus Cisplatin
Followed by Radical Liver Resection Versus Immediate
Radical Liver Resection Alone with or Without Adjuvant
Chemotherapy in Incidentally Detected Gallbladder
Carcinoma After Simple Cholecystectomy or in Front of
Radical Resection of BTC (ICC/ECC) – A Phase III Study
Utilizing The German Registry of Incidental Gallbladder
Carcinoma Platform (GR) – The AIO/ CALGP/ ACO- Gain-Trial –
Thorsten Götze 1; Ulli Simone Bankstahl 1; Wolf O. Bechstein 2; Tobias Keck 3;
Alfred Königsrainer 4; Sven A. Lang 5; Pompiliu Piso 6; Arndt Vogel 7;
Salah-Eddin Al-Batran 1
1Institut für Klinisch-Onkologische Forschung (IKF), Krankenhaus Nordwest
gGmbH, Frankfurt, Deutschland
2Klinik für Allgemein- und Viszeralchirurgie , Universitätsklinikum Frankfurt,
Frankfurt am Main, Deutschland
3Klinik für Chirurgie, Universitätsklinikum Schleswig-Holstein, Lübeck,
Deutschland
4Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinik
Tübingen, Tübingen, Deutschland
5Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg,
Freiburg im Breisgau, Deutschland
6Klinik für Allgemein- und Viszeralchirurgie, Barmherzige Brüder Regensburg ,
Regensburg, Deutschland
7Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische
Hochschule Hannover, Hannover, Deutschland
Purpose: Currently, complete surgical resection represents the only po-
tentially curative treatment option for Biliary Tract Cancer (BTC) includ-
ing Gallbladder Cancer (GBC). Even aer curative resection, 5-year OS
is only 20–40%. Gallbladder carcinoma is relatively rare, but still the h
most common neoplasm of the digestive tract and even the most frequent
cancer of the biliary system. Gallbladder carcinoma is suspected preop-
eratively in only 30% of all pts, while the majority of cases are discovered
incidentally by the pathologist aer cholecystectomy for a benign indica-
tion. For improving curative rates in BTC and GBC, early systemic ther-
apy combined with radical resection seems to be a promising approach.
e earliest moment to apply chemotherapy would be in front of radical
surgery. e encouraging results of neoadjuvant/perioperative concepts in
other malignancies provide an additional rationale to use this treatment
in the early phase of GBC management and even ICC/ECC. Especially
because data regarding pure adjuvant chemotherapy in BTC`s are con-
icting.
Methods: is is a multicenter, randomized, controlled, open-label phase
III study including pts with incidentally discovered GBCs aer simple
cholecystectomy in front of radical liver resection and pts with resect-
able/ borderline resectable cholangiocarcinomas (ICC/ ECC) scheduled
to receive perioperative chemotherapy (Gemcitabine + Cisplatin 3 cycles
pre- and post-surgery) or surgery alone followed by a therapy of investiga-
tors choice. Primary endpoint is OS; secondary endpoints are PFS, R0-re-
section rate, toxicity, perioperative morbidity, mortality and QoL. A total
of N=333 patients with GBC or BTC will be included. Recruitment has
started in August 2019. ClinicalTrials.gov ID: NCT03673072; EudraCT
number: 2017-004444-38
Disclosure Statement: No relevant disclosures.
820
The Intratumoral and IntestinalMicrobiome in Pancreatic
Cancer
Melanie Langheinrich 1, Stefan Wirtz 2, Georg Weber 1, Robert Grützmann 1,
Stephan Kersting 1
1Klinik für Chirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
2Medizinische Klinik I, Universitätsklinikum Erlangen, Erlangen
Purpose: e intestinal and even intratumoral microbiome is just be-
ginning to be recognized as an important player in carcinogenesis. Re-
cently, it has been shown that modulation of the intratumoral pancreatic
microbiome with antibiotics can alter the response to chemotherapy and
bacterial dysbiosis inuences PDA progression. erefore, identication
of microbiota within the tumor and in the adjacent compartments might
prove useful for future therapy.
Methods: Since 1/2019 we intraoperatively obtained tissue and uid sam-
ples from 30 patients with previously untreated pancreatic cancer. Micro-
biota proles were characterized by amplication of the V3/V4 region of
the 16SrRNA gene followed by deep sequencing and biostatistical analysis.
Results: Characteristic signatures for intratumoral and duodenal as well
as bile samples were obtained. e intraindividual comparison showed
only a partial overlap of the microbiota from these three compartments,
suggesting an enrichment or immune evasion of specic microbiota in
the tumor tissue. Cluster tree analysis based on the relative abundance
of OTUs revealed no signicant segregation of the bacterial microbiota
structures from pancreatic cancer patients. Some bacterial taxa were dif-
ferentiated between the pancreatic cancer patients at the taxonomy level
of genus or higher such as Acinetobacter, Oceanobacillus, Rahnella, Delf-
tia, and Sphingobium.
Conclusions: Microbial dysbiosis can drive PDAC progression by pro-
moting immune tolerance and targeting the microbiome can reverse this
process. We found that PDA is associated with a distinct stage- specic gut
and pancreatic microbiome that could drive disease progression by induc-
ing intratumoral immune suppression. Conversely, targeting the microbi-
ome could protected against PDA and enhanced antitumor immunity and
susceptibility to immunotherapy. Due to the potentially modiable nature
of gut bacteria a better understanding of the microbiome in pancreatic
cancer may lead to a microbiota based intervention during postoperative
clinical management.
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2018
833
Nephron-Sparing Surgery in Solitary Kidney Tumors
Alexey Kalpinskiy 1; Fidan Ashyrova 1; Nicolay Vorobyev 1;
Albina Muhomedyarova 1; Ivad Taraki 1; Andrey Kaprin 1
1Moskau, P. Hertsen Moscow Oncology Research Institute – Branch of the
National Medical Research, Moscow, Russland
Purpose: To assess the oncological and long term functional results of
nephron sparing surgery in patients (pts) with solitary kidney tumors.
Methods: 82 pts with solitary kidney tumor who had undergone partial
nephrectomy in the National Medical Research Center of Radiology were
analyzed. e mean age was 60.3 (29-77) years. Ratio of men to wom-
en was 2.4:1. e reasons for the absence of a contralateral kidney were
primary multiple metachronous renal cell cancer in 69 pts (84.3%), renal
hypoplasia - 7 (8.5%) pts, horseshoe kidney - 2 (2.4%) pts, hydronephro-
sis - 1 (1-2%) pts, urolithiasis -1 (1.2%) pts, pyelonephritis -1 (1.2%) pts,
polycystic kidney-1 (1.2%) pts. Median sum RENAL score was 6 (4-12).
Median preoperative glomerular ltration rate (GFR) was 56 (31-91) ml/
min/1.73m2. Median follow up time was 54 (6-147) months.
Results: Open partial nephrectomy was performed 71 (86.6%) pts and
laparoscopic partial nephrectomy - 10 (12.2%), and radiofrequency ab-
lation - 1 (1.2%) pts. Median postoperative GFR was 50.6 (24.6-98)
ml/min/1.73m2. Complication rate was 8.5%. Acute reduction in renal
function with immediate hemodialysis was required in 2 (2.4%) pts. Clear
cell renal cell carcinoma (RCC) was diagnosed in 69 (84.4%) pts, papillary
RCC types in 5 (6%) рts, chromophobe RCC in 4 (4.8%), mixed types
- in 1 (1.2%), angiomyolipoma in 1 (1.2%) pts, oncocytoma in 2 (2.4%)
pts. 5-year progression free survival was 57.5% and overall survival was
86.4%, cancer-specic survival - 87.8%. Local recurrence was detected in
6 (7.3%) pts and distant metastases in 17 (20.7%) pts. During follow up
period 8 (9.7%) pts were died and 6 (7.3%) from RCC progression. Sta-
tistically signicant correlation was revealed between pT stage (R = 0.33),
presence of sarcomatoid component (R = 0.28) and necrosis in tumor
(R = 0.25) and Fuhrman grade (R = 0.43) and probability of disease pro-
gression (p <0.05).
Conclusions: Partial nephrectomy of single kidney is an eective meth-
od of treatment of RCC with good long-term functional and oncological
results.
840
Surgery in Breast Cancer Liver Metastases - Essential Part of a
Multimodal Treatment?
Magdalena Menzel; Katharina Joechle; Andrea Klock;
Hannes Philipp Nee; Stefan Fichtner-Feigl; Sven A. Lang
Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie,
Freiburg im Breisgau, Deutschland
Purpose: About 10% of breast cancer patients present with metastatic dis-
ease at diagnosis, about 30% of patients will develop metastases at a later
time. In about half of these, metastatic spread occurs more than ve years
aer initial diagnosis, with Breast Cancer Liver Metastases (BCLM) being
the third most frequent site of metastatic spread (1). Usually, chemother-
apy and hormonal therapy are used as palliative treatment for metastatic
disease and patients are seldom considered for surgery.
Methods: We analyzed the outcome of 27 patients undergoing liver resec-
tion for BCLM between 1999 and 2018 at the Dpt. of Surgery, University
of Freiburg, using retrospective data. Survival analysis was performed in
SPSS.
Results: Median age at initial diagnosis was 48 (33-75). 23 patients (85%)
developed metachronous metastases with median time between initial
diagnosis and development of metastases of 5 yrs. (1-25 yrs.). 8 patients
(28.6%) also had extrahepatic disease at the time of BCLM diagnosis (os-
seus, pulmonal, cerebral). 77,8% of patients received a systemic treatment
(chemotherapy, antibodies, antihormonal therapy) at least 3 months prior
to surgery. Four patients (14%) showed disseminated disease intraopera-
tively and no resection was performed.
Perioperative morbidity was low, with one Clavien-Dindo Grade IV
(3,6%) and two Grade III (7.1%) complications. No perioperative mor-
tality occurred.
Median overall survival was 38 months, 5-yr OS 34.4% and 3-yr OS 59%.
Survival in the group of patients with R0/R1 resection was signicantly
higher (p=0,015) than in the group of patients with exploratory laparot-
omy/ R2 resection.
Conclusions: Lacking randomized controlled trials proving the benet,
surgical resection of BCLM is controversially discussed. Our small patient
collective covered 20 years with varying systemic treatment and dierent
surgical approaches - still, our results show an acceptable long-term sur-
vival, low morbidity and no mortality. Surgery for BCLM might be oered
to patients as part of multimodal therapy concepts.
860
Structural Analyses in Cell Junction Proteins after Associating
Liver Partition and Portal Vein Ligation for Staged
Hepatectomy
Hans-Michael Tautenhahn 1, 2; Sandra Brückner 3; Madlen Hempel 3;
Uta Dahmen 2; Utz Settmacher 2; Bruno Christ 3
1Research Programme „Else Kröner-Forschungskolleg AntiAge“, University
Hospital Jena, Jena, Deutschland
2Clinics of General, Visceral and Vascular Surgery, University Hospital Jena, Jena,
Deutschland
3Clinics of Visceral, Transplantation, Thoracic and Vascular Surgery, University
Hospital Leipzig, Leipzig, Deutschland
Purpose: Extended liver resections are frequently required for R0 resec-
tion margins in patients suering from liver tumors. One surgical tech-
nique to achieve a suciently functional liver volume is “Associating Liver
Partition and Portal vein ligation for Staged hepatectomy (ALPPS). It is,
however, rarely investigated and highly controversial, whether hypertro-
phy of the liver remnant increases functional liver parenchyma. e study
group characterized the liver parenchyma in dierent stages of the ALPPS
procedure. We focused on the integrity of cell-cell contacts, which we have
shown to correlate to liver function (Hempel et al. Cell Mol Life Sci. 2015).
Methods: e structural integrity of liver parenchyma was analyzed by
immunohistochemical detection of cell junction proteins ZO-1 and
E-cadherin. Apoptosis was evaluated by detection of activated Caspase 3.
In addition, (AST, ALT, bilirubin, µGT, INR, albumin) were analyzed until
the patients´ discharge.
Results: In all patients, transaminases peaked aer the rst and the sec-
ond surgical step of ALLPS. ZO-1 and E-cadherin was hardly detectable
at cell junctions in the ligated liver lobe indicating structural impairment.
In contrast, ZO-1 and E-cadherin were expressed physiologically at the
surface of hepatocytes in the hypertrophied liver remnant. In 1 patient,
nearly no ZO-1 and E-cadherin was expressed in the liver remnant in-
dicating functional impairment. Apoptotic events were observed in both
the ligated liver lobe and in the hypertrophied remnant. Whereas in the
ligated liver lobe Caspase 3 was detected in non-parenchymal cells, it was
more prominent in hepatocytes of the liver remnant.
Conclusions: Physiological ZO-1 and E-cadherin expression in the hy-
pertrophied liver tissue was detected in most patients, indicating struc-
tural and bona de functional integrity. Non-physiological expression in 1
patient might correlate with loss of function. is, however, needs conr-
mation by deeper functional analyses, e.g., by detection of plasma proteins
and metabolic enzymes in the remnant liver tissue.
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2018
Translational Oncology
Best-of-Abstracts-Vorträge
149
Mek Inhibitors Activate WNT Signalling and Induce Stem Cell
Plasticity in Colorectal Cancer
Tianzuo Zhan 1, 2; Giulia Ambrosi 2; Anna Maxi Wandmacher 2;
Benedikt Rauscher 2; Johannes Betge 1, 2; Niklas Rindtor 2;
Ragna S. Häussler 3; Isabel Hinsenkamp 1; Leonhard Bamberg 1;
Bernd Hessling 4; Karin Müller-Decker 5; Gerrit Erdmann 6;
Elke Burgermeister 1; Matthias P. Ebert 1; Michael Boutros 2
1Medical Faculty Mannheim, Heidelberg University, Department of Internal
Medicine II, Mannheim, Deutschland
2German Cancer Research Center (DKFZ), Division Signaling and Functional
Genomics, Heidelberg, Deutschland
3NMI Natural and Medical Sciences Institute at the University of Tübingen,
Reutlingen, Deutschland
4German Cancer Research Center (DKFZ), Proteomics Core Facility, Heidelberg,
Deutschland
5German Cancer Research Center, Core Facility Tumor Models, Heidelberg,
Deutschland
6NMI TT Pharmaservices, Berlin, Deutschland
Purpose: In colorectal cancer (CRC), aberrant Wnt signaling is essential
for tumorigenesis and maintenance of cancer stem cells. However, how
other oncogenic pathways converge on Wnt signaling to modulate stem
cell homeostasis in CRC currently remains poorly understood.
Methods: We performed large-scale compound screens to identify novel
pharmacological modulators of Wnt signaling in CRC cell lines. Cellular
activity of the Wnt pathway was measured using target gene expression
und Wnt reporters. e eect of candidate compounds was validated in
mouse models and dierent murine and human CRC organoid lines. e
eect of combination drug treatment was determined using a novel CRC
organoid derived xenogra model.
Results: e compound screens identied MEK inhibitors as potent ac-
tivators of Wnt/beta-catenin signaling in CRC. Targeting MEK increas-
es Wnt activity in dierent CRC cell lines and murine intestine in vivo.
Truncating mutations of APC generated by CRISPR/Cas9 strongly syner-
gized with MEK inhibitors in enhancing Wnt response in isogenic CRC
cell lines and murine colon organoid models. Mechanistically, we demon-
strate that MEK inhibition induces a rapid downregulation of AXIN1. Us-
ing patient-derived CRC organoids, we show that MEK inhibition leads
to increased Wnt activity, elevated LGR5 levels and enrichment of gene
signatures associated with stemness and cancer relapse. Furthermore,
co-treatment of MEK and Wnt inhibitors eciently reduce tumor growth
in vitro and in vivo.
Conclusions: Our study demonstrates that clinically used MEK inhibitors
inadvertently induce Wnt signaling and stem cell plasticity, revealing an
unknown side eect of RAS pathway inhibition.
References:
1. Zhan T*, Rindtor N*, Boutros M. Wnt signaling in cancer. Oncogene
2017;36:1461–73.
2. Zhan T*, Ambrosi G*, Wandmacher AM*, Rauscher B, Betge J, Rindtor N,
ussler RS, Hinsenkamp I, et al. MEK inhibitors activate Wnt signalling and
induce stem cell plasticity in colorectal cancer. Nat Commun 2019;10:2197
Disclosure Statement: No conict of interest.
598
NGS-Based Mutation Analysis of BRCA1-Associated Triple-
Negative Breast Cancers
Ellen Honisch 1; Rose Fröhlich 1; Anne-Sophie Vesper 2; Ines Beyer 2;
Tanja Fehm 2; Dieter Niederacher 1
1Universitätsklinikum Düsseldorf, Klinik für Frauenheilkunde und Geburtshilfe;
Molekulargenetisches Labor, Düsseldorf, Deutschland
2Universitätsklinikum Düsseldorf, Klinik für Frauenheilkunde und Geburtshilfe,
Düsseldorf, Deutschland
Purpose: Despite their common receptor status, triple-negative breast
cancer (TNBC) is increasingly presenting as genetically diverse disease.
About 15% of TNBCs are associated with a BRCA1 germline mutation.
Aim of this study is to identify genes involved in tumor development and
progression and to further characterize BRCA1-associated TNBCs by
NGS-based mutation analysis.
Methods: Macrodissected FFPE tissues were analysed with two NGS mul-
tigene panels: QiaSeq Human Breast Cancer panel (Qiagen) and TST170
gene panel (Illumina). By additional RNA analysis, TST170 not only de-
tects small DNA changes, but also amplications as well as splice and fu-
sion variants.
Results: TNBC tissue samples were available for 56 of 113 BRCA1 mu-
tation carriers identied in our breast and ovarian cancer center. Of 104
tissues received, 65 were processed. In 61 of these, tumor cell content
(>30%) was adequate. In 86% (48/56), isolated DNA was suciently
intact and ampliable, as determined by qPCR. In 20 of 21 tumor sam-
ples currently analysed, the respective BRCA1 germline mutation was
detected, with variant frequencies indicating loss of heterozygosity. Pre-
liminary data analysis revealed 37 SNVs /InDels rated as pathogenic. In
addition to single events in dierent genes, we observed frequent muta-
tions in KMT2C (11/11) and TP53 (17/21). For mutations in genes shared
by both panels, variant allele frequencies were similar. e TST170 panel
further detected four gene fusion events (BRCA1-STAT3, FGFR1-HFM1,
NOTCH1-CPA6, TACC3-FGFR2) and an EGFR splice variant.
Conclusions: In combination, both multigene panels enable the detec-
tion of a broad spectrum of diverse variant types in dierent genes. is
could help identifying mutations with prognostic or predictive relevance
in BRCA1-associated TNBCs.
Poster
86
Reprograming of Innate Immunity by Tumor-Derived R-2-
Hydroxyglutarate
Mirco Friedrich 1; Lukas Bunse 1, 2; Roman Sankowski 3; Edward Green 1;
Theresa Bunse 1, 2; Michael Kilian 1; Stefan Pusch 4; Andreas von Deimling 4;
Marco Prinz 3; Michael Platten 1, 2
1Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland
2Neurologische Klinik, Universitätsklinikum Mannheim
3Institut für Neuropathologie, Universitätsklinikum Freiburg
4Institut für Neuropathologie, Universitätsklinikum Heidelberg
Purpose: Isocitrate dehydrogenase 1 (IDH1)-mutant tumors form bi-
ologically distinct subgroups in acute myeloid leukemia and low-grade
gliomas. Mutations in the tumor-dening enzyme IDH1 result in the in-
creased production of R-2-hydroxyglutarate (R-2-HG) and constitute a
distinct, metabolically skewed biological entity. ese tumors are associ-
ated with less abundant and phenotypically altered immune cell inltrates
compared to IDH1 wild-type tumors. Despite recent advancements, the
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2018
mechanisms shaping the immune microenvironment of IDH1-mutated
tumors remain elusive.
Methods & Results: We could show that IDH1-mutated gliomas subdue
their innate immune microenvironment by prompting a multifaceted
reprogramming of myeloid cell metabolism. Integrated single-cell tran-
scriptomic and proteomic analyses of human control and glioblastoma
samples identied myeloid cell subsets with distinct fates in IDH1-mutat-
ed glioma that diverge from canonical trajectories of antigen-presenting
cells. Paracrine tumor-derived R-2-HG, when transported into macro-
phages, induced an immunosuppressive state through dysregulated tryp-
tophan metabolism and subsequent activation of the aryl hydrocarbon
receptor (AHR), resulting in increased production of IL-10 and TGF-β,
down-regulation of MHC-II expression, and consequent suppression of T
cell activity. We demonstrate that eective immunotherapy in the context
of mutant IDH1 requires normalization of this AHR-mediated phenotype.
Conclusions: ese ndings argue for the development of new immuno-
therapy concepts that recognize the cell-specic immunomodulatory ef-
fects of IDH1-mutated tumors; and could prove vital dening the relevant
entities targeted by small molecule AHR inhibitors currently undergoing
preclinical development.
Reference:
1. Dang, L. et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.
Nature 462, 739–44 (2009).
Disclosure Statement: I have no nancial relationships to disclose.
112
Oncogenic Potential of Rare Mutations in RRAS2
David Feuersinger 1, 2; Raaela Bung 1, 2; Cihan Erkut 1; Priya Chudasama 3;
Thomas Longerich 4; Moritz Jesinghaus 5; Wilko Weichert 5;
Malgorzata Oles 6; Stefanie Reinhart 1; Dorothee Terhardt 1; Peter Horak 6;
Simon Kreutzfeldt 6; Sandrine Sander 7; Stefan Fröhling 6; Claudia Scholl 1
1Division of Applied Functional Genomics, German Cancer Research Center
(DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg,
Deutschland
2Faculty of Biosciences, Heidelberg University, Heidelberg, Deutschland
3Division of Precision Sarcoma Research, DKFZ and NCT Heidelberg, Heidelberg,
Deutschland
4Institute of Pathology, University Hospital Heidelberg, Heidelberg, Deutschland
5Institute of Pathology, Technical University Munich, Munich, Deutschland
6Division of Translational Medical Oncology, DKFZ and NCT Heidelberg,
Heidelberg, Deutschland
7Division of Adaptive Immunity and Lymphoma, DKFZ and NCT Heidelberg,
Heidelberg, Deutschland
Purpose: e small GTPase RRAS2 is aected by low-frequency muta-
tions in codons 23 and 72 in cancers of dierent tissue origin, including
germ cell tumors. e contribution of these rare mutations to oncogenesis
is unknown. e aim of this project is to understand the biology and on-
cogenic eects of RRAS2 mutations and to identify mutant RRAS2-specif-
ic vulnerabilities for therapeutic exploitation.
Methods: We engineered isogenic cell lines by lentiviral cDNA transfer
of RRAS2 variants into immortalized human breast cells (MCF10A) and
murine yolk sac cells (C166). ese isogenic cell lines were phenotypi-
cally characterized by colony formation, proliferation, and so agar as-
says. Genes and pathways responsive to mutant RRAS2 expression were
investigated by western blot and RNA sequencing. Furthermore, we used
a transgenic mouse model with global expression of mutant RRAS2 to
study oncogenic eects in vivo.
Results: RRAS2 mutations in codons 23 and 72 strongly induced
anchorage-independent growth in MCF10A and C166 cells and EGF-
independent growth of MCF10A cells in colony formation assays. No
signicant proliferation changes were observed in either cell line when
cultured in complete growth medium. Transcriptional proling of RRAS2-
mutant MCF10A cells revealed several deregulated pathways associated
with cancer, most prevalently activation of the MAPK and PI3K pathways
and induction of genes involved in epithelial-to-mesenchymal transition.
Correspondingly, mutant RRAS2 increased phosphorylation of Erk1/2
and Akt in C166 cells. In vivo, global expression of mutant RRAS2 resulted
in highly aggressive pancreatic ductal adenocarcinoma and preneoplastic
lesions in the lung aer two weeks.
Conclusions: We identied strong oncogenic eects of RRAS2 mutations
in vivo and in vitro in cells from dierent tissue origin that correspond
to primary tumor samples, reinforcing the importance of rare mutations
as cancer drivers. ese ndings might open up opportunities for new
therapeutic approaches.
141
B Cells Sustain Inammation and Predict Response to Immune
Checkpoint Blockade in Human Melanoma
Johannes Griss 1, Wolfgang Bauer 1, Christine Wagner 1,
Katharina Grabmeier-Pstershammer 2, Peter Steinberger 2,
Stephan Wagner 1
1Dept. of Dermatology, Medical University Vienna, Vienna, Österreich
2Insitute of Immunology, Medical University Vienna, Vienna, Österreich
Purpose: Tumor inammation predicts response to immune check-
point blockade in human melanoma. Established mechanisms of therapy
response center on anti-tumor T cell responses. Here we show that tu-
mor-associated B cells (TAB) are vital to tumor inammation.
Methods: We used whole RNA-seq and (phospho)proteomics data from
human peripheral blood- and tumor-derived B cells, whole and single cell
(sc) RNA-seq and multiplex immunostaining data from human melano-
mas and a surrogate in vitro assay of T cell activation.
Results: In human melanoma, TAB are located at the invasive tumor-stro-
ma margin arguing for a preferentially cell contact-independent com-
munication with tumor cells. We therefore exposed in vitro peripheral
blood- and melanoma-derived B cells to the secretome from autologous
melanoma cells. In proteomics and RNA-seq data, we observed induc-
tion of pro- and anti-inammatory factors and dierentiation towards a
plasmablast-like phenotype. We could nd this B cell phenotype as a dis-
tinct B cell cluster in public scRNA-seq data as well as by 7 color multiplex
immunostaining of human melanomas (1).
Depletion of TAB by anti-CD20 immunotherapy of metastatic mela-
noma patients led to a pronounced decrease in tumor inammation sig-
natures and CD8+ T cell numbers, in line with scRNA-seq data on expres-
sion of T cell chemoattractants CCL3,4,5 in plasmablast-like TAB.
Interestingly, the frequency of plasmablast-like TAB in pretherapy
melanoma samples predicted response and survival to immune check-
point blockade in two independent large-scale clinical (sc)RNA-seq data-
sets. Consistently, melanoma secretome-induced B cells signicantly in-
creased the activation of PD1-expressing Jurkat T cells by PD1 blockade
in vitro.
Conclusions: Together, our data argue that tumor-associated B cells or-
chestrate and sustain tumor inammation, recruit CD8+ T eector cells
and may represent a predictor for response and survival to immune
checkpoint blockade in human melanoma.
Reference:
1. doi.org/10.1101/478735
Disclosure Statement: Supported by the FWF-Austrian Science Fund.
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197
Evaluation of the Transsectoral Cooperation and Educational
Program of the Cologne Department of the German
Consortium for Hereditary Breast and Ovarian Cancer (GC
HBOC) for Certied Breast and Gynecological Cancer Centers
Natalie Herold; Kathrin Bredow; Eric Hahnen;
Barbara Wappenschmidt; Jan Hauke; Regina Wiedemann; Anke Waha;
Britta Blümcke; Esther Pohl-Rescigno; Kerstin Rhiem; Rita Schmutzler
Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology
(CIO), Cologne
Purpose: Relevant familial cancer history concerns about 30% of all pa-
tients with breast and ovarian cancer. us, genetic counseling of these
patients and their families is an important topic. To meet the challenges of
germline gene panel analyses and the clinical translation of the test results,
we established a structured and standardized educational program (EP)
for physicians of certied breast and gynecological cancer centers within
a transsectoral cooperation (TC) in 2015. e EP covers curricula with
written exams and a practical training.
Methods: To date we performed 24 curricula, which covered topics from
identifying persons at risk over genetic counseling and interpretation of
genetic test results to risk-adjusted preventive measures and targeted ther-
apies. To evaluate these curricula, we used an in-house survey and a stan-
dardized survey of the Ärztekammer Nordrhein (AekNo). To evaluate the
TC we performed a survey among 79 physicians.
Results: A total of 235 in-house survey results were evaluated. We in-
quired the structure and comprehensibility of the curricula (1.57; scale 1
to 6, analogue to German school grades), presence of all clinically relevant
information (1.58), and relevance for daily clinical counseling (1.61). Sim-
ilar results arise from the survey of the AekNo.
e TC was evaluated by 37 of 79 physicians. A total of ten items could
be rated. 81% stated a very good or good organization of the program,
ow of information (86%), clarity of genetic reports (86%), and 100% a
very good quality of our cancer prevention and therapy concept (scale:
very good, good, acceptable or insucient).
Conclusions: Participants stated a high or very high satisfaction with our
curricula and TC. It assists highly specialized clinicians in genetic coun-
seling, in clinical management of patients at high risk (e.g. participation
in evidence-based risk-adjusted prevention programs) and in acquiring
clinical data in knowledge-generating medicine. e GC-HBOC and the
German Cancer Society currently implement the EP nation-wide.
260
Establishing an IT-Supported Molecular Tumor Board in the
Routine Setting –A Report from the Cancer Center Heilbronn-
Franken
Uwe Martens 1, 2; Dilyana Vladimirova 1; Sylvia Bochum 2, 3;
Antonella Schilliro 1; Dora Finkeisen 2; Daniel Zsebedits 2; Saskia Biskup 4;
Christian Fegeler 2
1SLK-Kliniken Heilbronn GmbH / Klinikum am Gesundbrunnen, Klinik für Innere
Medizin III, Heilbronn, Deutschland
2MOLIT Institut für personalisierte Medizin gGmbH, Heilbronn, Deutschland
3SLK-Kliniken Heilbronn GmbH / Klinikum am Gesundbrunnen , Tumorzentrum
Heilbronn-Franken, Heilbronn, Deutschland
4CeGaT GmbH, Tübingen, Deutschland
Purpose: e increasing practicality of genomic sequencing technology
has led to its incorporation into routine clinical practice. To strengthen
implementation of genomics-guided cancer therapies, a Molecular Tumor
Board (MTB) and a supporting IT-frame work (VITU) have been imple-
mented at the Cancer Center Heilbronn-Franken in 2017.
Methods: A team comprising oncologists, genetic counselors and basic
scientists meets weekly to discuss each case reviewing clinical and scien-
tic evidence in the context of the tumor entity. To assist physicians, an
individual report summarizing genetic aberrations and ranked treating
options is generated. External experts and resident oncologists are able
to participate via web-based video conferencing, and a newly developed
open-source IT tool (VITU) is used for process and data management.
Results: Since 2017 more than 160 cases have been evaluated in the MTB.
In 50% of all cases a molecular stratied treatment based on tumor genetic
prole was recommended, with 15% of patients subsequently treated with
MTB-recommended personalized targeted agents, and for another 15%
targeted agents serve as an option in case of future progression. Inclusion
in a clinical trial was possible for 3% of all patients. Furthermore, a data-
base has been established enabling management and analysis of genomic
and clinical data and outcome to optimize clinical benet.
Conclusion: Molecular characterization is feasible in the routine setting
and provides new treatment options for a substantial portion of cancer
patients. However, patient-centered interpreting of variants still remains a
challenge and, therefore, the implementation of a interdisciplinary MTB
is of central importance. Novel IT-supported decision support tools and
data sharing eorts will be crucial to exploit the full potential of com-
prehensive molecular cancer diagnostics. e digitization of processes
supports the collaboration of experts and the practicality of routine op-
erations in the hospital.
Disclosure Statement: No conict of interest was reported by the authors.
334
Unraveling Intra-Tumor Heterogeneity in Colorectal Cancer
Using Oncoproteomics in Patient-Derived Organoids
Ulrike Pfohl 1; Patrick Herter 2; Sanam Bashir 3; Gerrit Erdmann 4;
Guido Gambara 5; Johannes Haybäck 6; Ralf Kühn 3; Soulafa Mamlouk 5;
Alessandra Silvestri 7; Markus Templin 2; Christian Regenbrecht 7
1Otto-von-Guericke-Universität Magdeburg, Magdeburg, Deutschland
2Natural and Medical Science Institute at the University of Tübingen,
Reutlingen, Deutschland
3Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Deutschland
4NMI - TT Pharmaservices, Berlin, Deutschland
5Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin,
Berlin, Deutschland
6Institut für Pathologie, Universitätsklinikum in Magdeburg, Magdeburg,
Deutschland
7Cellphenomics GmbH, Berlin, Deutschland
Purpose: Intra-tumor heterogeneity (ITH) poses a major obstacle in can-
cer therapy. In colorectal cancer (CRC), mutations in the transforming
growth factor-β (TGF-β) pathway, especially in SMAD4 gene, have been
correlated with decreased overall survival and are suspected to modulate
chemoresistance. We have previously shown that SMAD4R361H is associat-
ed with dierential drug response towards EGFR, MEK and PI3K inhibi-
tors. In the present study, we uncover the mechanistic role of SMAD4R361H
using oncoproteomics in isogenic CRISPR-engineered SMAD4R361H, CRC
patient-derived organoids (PD3D®).
Methods: Here, we investigated multiple organoid cultures from a sin-
gle CRC and its liver metastasis. Targeted amplicon sequencing identi-
ed the SMAD4R361H mutation in 2/5 subcultures. Using CRISPR-Cas9
approach, we introduced the SMAD4R361H into the wildtype organoids.
Organoid cultures were subjected to a comparative drug screening and
subsequent multiplex protein proling analysis (DigiWest®) with a panel
of >100 (phospho-)proteins on cancer-specic cellular pathways at vari-
ous timepoints.
Results: SMAD4R361H organoids showed a dierential response to EGFR
and MEK inhibition compared to their SMAD4 wildtype counterparts.
Protein proling revealed dierent levels of Wnt pathway activation under
treatment, while showing only minor dierences upon MEK inhibition in
the downstream signaling cascade. Early results point towards an initial
cell cycle arrest for growth inhibition.
Conclusions: PD3Ds recapitulate the genetic and phenotypic
heterogeneity of the donor tumor tissue. We show that SMAD4R361H
contributes to the sensitivity towards trametinib in vitro. e combination
of multisampling, characterization and CRISPR is not limited to studying
the role of the R361H mutation. It has a broad range of applications in
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understanding cancer biology, ITH, drug response and may help to
improve therapy response prediction in cancer patients.
Disclosure Statement: ere is nothing to disclose.
362
A ‘Beyond Genomics’ Approach to Precision Oncology: A
Multiplex Protein Proling Platform for Tumor and Tumor
Organoid Samples
Gerrit Erdmann 1; Anja Arndt 1; Przemyslaw Dudys 1; Ulrike Pfohl 2;
Markus Templin 3; Christian Regenbrecht 2, 4; Christoph Sachse 1
1NMI TT Pharmaservices, Berlin, Deutschland
2Institute of Pathology, University Clinic Magdeburg, Magdeburg, Deutschland
3NMI Natural and Medical Sciences Institute at the University of Tübingen,
Reutlingen, Deutschland
4ASC Oncology, Berlin, Deutschland
Purpose: Precision medicines goal of achieving a better response rate
by avoiding ineective therapies has sparked new approaches, including
the testing of patient-derived 3d (PD3Ds) tumor cultures for modeling
individual patient response, and the use of various molecular pathology
techniques for advanced tumor proling. However, well-established ge-
nomics methodologies cannot directly assess cell-signaling activity within
the tumor cells dened by the phosphorylation status of cellular signaling
pathway networks.
Methods: Here we present the development of a robust protein proling
strategy utilizing the DigiWest immuno-assay platform, to obtain data on
the activation status of key cellular signaling networks implicated in can-
cer, and on proteins targeted by FDA-approved drugs including a number
of targeted cancer therapies for e.g. EGFR, HER2, PI3K, mTOR, ALK and
AKT.
Results: We compiled a list of relevant pathway nodes and their phos-
phorylation sites that yield activity information on RAS/RAF/ERK, PI3K/
AKT and mTOR signaling pathways. Based on this, we validated 242 total
and phospho antibodies in a pre-set oncoproteomic DigiWest panel that
yields information on the activity of these signaling networks from the
receptor level down to transcription factors, apoptosis and proliferation.
is oncoproteomic panel can be utilized for elucidating drug response
in pre-clinical cell models, in PD3D organoid models or in clinical tumor
samples. Exemplary, we show dierential eects of PI3K kinase inhibitor
copanlisib vs MEK inhibitor trametinib at various levels within their sig-
naling networks. Also, we tested this panel in PD3D organoids that were
subjected to screening against common targeted therapies.
Conclusions: While the initial results are promising, further work on
evaluating how such an oncoproteomic panel proling might contribute
to the rationale for personalized therapy decisions is required.
Disclosure Statement: NMI TT Pharmaservices oers DigiWest protein proling
as a service.
578
Preclinical Case Study: Patient-Derived Head and Neck Cancer
Xenograft on Mice Humanized with Autologous and Allogene
Immune Cells, A Model for Personalized Immuno-Oncology
Research
Maria Stecklum 1; Konrad Klinghammer 2; Annika Wulf-Goldenberg 1;
Bernadette Brzezicha 1; Korinna Jöhrens 3; Jens Homann 1
1EPO Experimentelle Pharmakologie & Onkologie Berlin-Buch GmbH, Berlin,
Deutschland
2Charité Universitätsmedizin Berlin Campus Benjamin Franklin, Berlin,
Deutschland
3Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Deutschland
Purpose: Models for the preclinical evaluation of novel immune
modulators for cancer treatment require engrament of human tumor
with a matching immune cell population. In this case study, we established
a patient-derived xenogra (PDX) from a head and neck squamous cell
cancer (HNSCC). In parallel patients blood samples were collected.
Mice with engraed HNSCC PDX, were humanized with patients
PBMC. By this we successfully generated a patient-specic human tu-
mor-immune cell model in mice with 100% HLA-match. Model develop-
ment included the comparison of PDX engrament on mice with either
HLA- or non HLA-matching PBMC’s from dierent donors or on human-
ized mice generated by HSC transplantation.
Finally, we validated the model by comparing treatment eects with
the checkpoint inhibitor Nivolumab.
Methods: e HNSCC PDX were transplanted on NOG mice. Aer tu-
mor engrament mice were randomized in 6 groups, receiving PBMCs i.v.
either from the patient or from 5 well characterized donors. Furthermore
NOG mice were humanized with HSC from 5 donors. Blood and tumor
samples were analysed by FACS and IHC.
Results: In the autologous PBMC model, no interference with the prolif-
eration of the PDX was seen. However, on mice humanized with donor
PBMC’s with a high HLA match, a stimulation of tumor proliferation was
observed. Surprisingly, treatment with Nivolumab did not induce a sig-
nicant tumor growth inhibition in the autologous model. On the mice
humanized with PBMC and HSC from dierent donors, we observed a
correlation of treatment eects with HLA match. Finally, inltrating im-
mune cells were detected in the tumors.
Conclusions: We developed a humanized immune-PDX model enabling
appropriate preclinical translational research on tumor immune biology
and the evaluation of new therapies and combinations, as well as the iden-
tication and validation of biomarkers for immune therapy. Furthermore,
results showed a correlation between immune therapy eect and HLA
matching in preclinical models.
Disclosure Statement: I’m a full-time employee at EPO GmbH.
615
Phenotypic and Functional Characteristics of Preclinical
Breast Cancer Models
Annika Wulf-Goldenberg 1; Verena Kiver 2, 3; Bernadette Brzezicha 1;
Philipp Jurmeister 4; Caroline Schweiger 2, 5, 6; Jens-Uwe Blohmer 3;
Ulrich Keilholz 2, 5, 6; Jens Homann 1
1EPO Experimentelle Pharmakologie & Onkologie Berlin-Buch GmbH, Berlin,
Deutschland
2Charité Comprehensive Cancer Center, Berlin, Deutschland
3Charite - Campus Mitte Klinik für Gynäkologie, Berlin, Deutschland
4Charite - Campus Mitte Institut für Pathologie, Berlin, Deutschland
5Deutsches Krebsforschungszentrum, Heidelberg, Deutschland
6Deutsches Konsortium für Translationale Krebsforschung, Berlin, Deutschland
Purpose: Generation of patient-derived models for breast cancer is di-
cult and the success is oen low compared to other histologies. With the
goal to develop a resource for testing novel compounds and combinations
for treatment of refractory breast cancer, we established patient-derived
xenogra models (PDX) from tumors clinically unresponsive to at least
anthracyclines, platins and taxanes. Here we report phenotypic charac-
terization and drug testing data of our established breast cancer models.
Methods: Breast cancer tissue samples were engraed on immunode-
cient NOG mice. e tissues were obtained from patients with disease
progression aer chemotherapy with three to four drugs. e established
PDX were characterized by immunohistochemistry and are currently un-
dergoing exome and transcriptome sequencing. e PDX were tested for
response to all standard chemotherapy agents. e drug testing included
platins, taxanes, anthracyclines, 5-FU, everolimus, eribulin and depend-
ing on the subtype tamoxifen, olaparib, and a CDK4/6 Inhibitor.
Results: 50 breast cancer samples have been processed under rapid and
stringent conditions. Currently eight models, six TNBC and two hormone
receptor positive PDX, have been fully engraed, phenotypically charac-
terized and drug screened. e immunohistochemistry stainings for es-
trogen/progesterone/androgen/Her2 receptors, Ki-67, and CK5/6 of the
original tumor and the PDX were comparable. All patients had shown
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clinical resistance to platin, anthracyclines, and taxanes in the neoadju-
vant or palliative setting. Concordant with the clinical resistance, the PDX
models showed only limited or transient sensitivity to single agents.
Conclusions: With our stringent approach, we successfully generated 8
new breast cancer PDX models (16% take). e phenotype between pa-
tient tumors and PDX was consistent. e minor dierences in respon-
siveness to chemotherapy may be due to dierences in stromal factors. In
summary, the PDX of refractory tumors are a versatile resource for pre-
clinical studies of novel treatment approaches.
675
Changes in the Number of Circulating Epithelial Tumor Cells
(CETCS) During Radiotherapy (RT) In Patients with Breast
Cancer
Dorothea Schott 1; Monika Pizon 1; Ulrich Pachmann 1;
Katharina Pachmann 1; Matthias Mäurer 2
1Transfusion Center Bayreuth, Bayreuth, Deutschland
2Universitätsklinikum Jena, Klinik für Strahlentherapie und Radioonkologie,
Jena, Deutschland
Purpose: Circulating tumor cells represent the liquid component of solid
tumors and are a surrogate marker for residual cancer burden. RT reduces
not only local recurrence but also improves overall survival by preventing
distant metastases, which indicates its inuence on the remaining occult
tumor. Detection of CETCs may monitor the therapeutic eect in breast
cancer patients. ere is limited data on the changes of CETC numbers
during radiotherapy in patients aer neoadjuvant chemotherapy.
Methods: CETCs were analyzed prior to (baseline), 3 and 6 weeks aer
the start of RT in 54 primary breast cancer patients in early and locally ad-
vanced stages aer adjuvant or neoadjuvant chemotherapy. e number
of CETCs was investigated using the maintrac method.
Results: Patients with triple negative breast cancer had statistically sig-
nicantly more CETCs as compared to patients with luminal A and B
subtypes. Furthermore, patients treated with adjuvant chemotherapy had
statistically signicantly less CETCs as compared to patients who received
neoadjuvant chemotherapy (median 9 vs. 22, p<0.05). Interestingly, the
number of CETCs was continuously reduced during RT in patients aer
neoadjuvant chemotherapy but not aer adjuvant chemotherapy. e -
nal median numbers (aer RT) of CETCs were not signicantly dierent
between patients in the neoadjuvant and adjuvant setting.
Conclusions: Although the number of CETCs was higher in patients who
had received neoadjuvant chemotherapy, radiotherapy reduced CETCs
but the same was not observed in patients who had received adjuvant che-
motherapy. e clinical impact of this result needs to be analyzed in the
future.
Disclosure Statement: We declare that we have no conict of interest.
687
The CCC Munichlmu Molecular Tumor Board: Clinical and
Molecular Characteristics of the First 450 Patients
Kathrin Heinrich 1; Lisa Miller-Phillips 1; Michael von Bergwelt-Baildon 1;
Klaus Metzeler 1; Julian Holch 1; Rachel Würstlein 2; Andreas Jung 3;
Volker Heinemann 1; Thomas Kirchner 3; Benedikt Westphalen 1
1Medizinische Klinik und Poliklinik III, Klinikum der Universität München,
München, Deutschland
2Brustzentrum und CCC München, Klinik und Poliklinik für Frauenheilkunde und
Geburtshilfe, Klinikum der Universität München, München, Deutschland
3Pathologisches Institut der LMU, Ludwig-Maximilians-Universität München,
München, Deutschland
Purpose: To establish a precision oncology program at University of
Munich, the Molecular Tumor Board (MTB) was implemented in 2016.
Now the rst comprehensive review of cases was done to assess the clinical
implications and utility of the program.
Methods: Charts, mutational spectra and tumor board decisions of the
rst consecutive 450 cases were reviewed. Descriptive statistics were ap-
plied to describe relevant ndings.
Results: Of the 450 patients originally referred for Next Generation Se-
quencing (NGS), 406 underwent molecular diagnostics. In most cases
(n=332) genetic analyses were performed on tumor tissue, in 27 cases
cerebral spinal uid was used for NGS. In 28 patients the analysis was
performed on liquid biopsies taken from peripheral blood, in 2 patients,
liquid biopsies were taken from malignant ascites. In 337 patients, diag-
nostics were technically successful. Unsuccessful tests were mostly due
to insucient amount or low quality of the provided tissue. In 309 cases
(75%), a molecular alteration was identied, which was potentially drug-
gable in over 75% (n=204).
Conclusions: e MTB has experienced a rapid growth in case numbers.
With a broad range of dierent malignant diseases analyzed, the program
serves as a clinical tool for patients from a variety of departments within
the University of Munich. Based on our initial results patients with certain
tumor entities seem to benet more from extended molecular diagnostics.
Still, access to targeted treatments outside of clinical trials is a major ob-
stacle in precision oncology.
Reference:
1. Holch et al. Universal Genomic Testing: e next step in oncological decisi-
on-making or a dead end street? Eur J Cancer 2017; 82:72-79
Disclosure Statement: No relevant nancial disclosures with regard to this
abstract.
701
Algorithm for Investigating Cell-CellCommunicationin
Malignant and Healthy Bone MarrowUsingSCRNAseqData
Maria Solovey 1, Frank Ziemann 2, Klaus H. Metzeler 2, Antonio
Scialdone 1, 3, 4
1ICB, Helmholtz Zentrum München, Neuherberg, Deutschland
2Klinikum der Universität München, Medizinische Klinik und Poliklinik III,
München, Deutschland
3IFE, Helmholtz Zentrum München, Neuherberg, Deutschland
4IES, Helmholtz Zentrum München, München, Deutschland
Purpose: Intercellular communication plays an essential role in the
proper functioning blood homeostasis in the bone marrow and its alter-
ation might contribute to development and maintenance of malignant
neoplasms. In our project, we aim at developing an algorithm to assess
the cell-cell communication between distinct cell types using single-cell
RNAseq data. While several algorithms have been published lately, their
results are oen hard to visualize and interpret.
Methods: In our algorithm, we use new visualization and classication
tools based on multiplex networks and network clustering strategies. As
an example, we apply our algorithm to a single cell RNAseq data set (van
Galen et al., 2019) that is publicly available.
Results: We analyzed benign bone marrow samples as well as several
AML patients with serial time-points available and dierent treatment
modalities (intensive induction chemotherapy or acazitidine + veneto-
clax). By this we could identify new lines of intercellular communication
that change during malignant transformation and can be reestablished by
treatment of the AML. In addition, we were able to show how dierent
treatment modalities impact on intercellular communication and which
intercellular communication could be important for benign bone marrow
function.
Conclusion: ese ndings will serve as a basis for further biological val-
idation of the found communication lines in vivo and show how existing
data sets can be used to establish new data driven hypothesis for a deeper
understanding of hematopoietic neoplasms.
Reference:
1. van Galen, P., Hovestadt, V., Wadsworth, M. H., Ii, Hughes, T. K., Grin,
G. K., Battaglia, S., … Bernstein, B. E. (2019). Single-Cell RNA-Seq Reveals
AML Hierarchies Relevant to Disease Progression and Immunity. Cell, 176(6),
1265–1281.e24.
Disclosure Statement: No conict of interests.
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772
Increased Activity of Poly-Adp Ribose Polymerase (PARP) in
Peripheral Blood Lymphocytes Predicts Prostate Cancer Risk
Miriam Deniz 1; Friedemann Zengerling 2; Thomas W. P. Friedl 1;
Theresa Gundelach 1; Wolfgang Janni 1; Elisabeth Wiesmüller 1
1Universitätsklinik Ulm, Frauenklinik, Ulm, Deutschland
2Universitätsklinik Ulm, Klinik für Urologie
Purpose: Defects in Homologous Recombination (HR) as the most ac-
curate pathway for DNA-double-strand-break (DSB) repair are found in
various types of cancer. Dysfunction in HR can lead to an increase of oth-
er less precise DSB-repair mechanisms. is is associated with genomic
instability. So inherited and somatic mutations in susceptibility genes like
BRCA1, BRCA2, PALB1, RAD51C can be found in a high proportion of
breast- and ovarian cancer, as well as prostate cancer patients. Defects in
DSB-repair pathways are utilized as therapeutic option with drugs like
platinum-derivates and PARP inhibitors in prostate cancer as well as in
ovarian- and breast cancer patients. In previous case-control-studies we
found mutagenic DSB-Repair in peripheral blood lymphocytes (PBLs)
were associated with elevated risk for breast- and ovarian cancer, which
could be indicative of genetic predisposition.
Methods: We performed a case-control study to determine DSB re-
pair-functions in PBLs from 75 prostate cancer patients and 47 healthy
controls using the GFP-based test system established for pathogenic breast
and ovarian risk gene mutations. In parallel, we examined sensitivities to
Carboplatin and PARP inhibitors as well as PARP activities.
Results: Regarding PARP-activities in PBLs we detected a signicant
increase of basal (P = 0.001) and activated (P = 0.006) PARP activity in
cancer patients in comparison to controls. Additionally we found higher
sensitivities of PBLs from prostate cancer patients to carboplatin (P <
0.0001) and signicant decrease of SSA with increasing age in prostate
cancer patients (P = 0.004). Comparing DSB-repair activities and PARP-
inhibitor sensitivities between cancer patients and controls we did not
nd signicant dierences.
Conclusions: ese ndings demonstrates the potential of detecting PARP
activities in PBLs as method to estimate prostate cancer susceptibility.
Furthermore measurement of carboplatin-sensitivities and DSB-repair-
activities might have the potential to further classify patients individually
risk.
794
NovelPatient-Derived Xenografts (PDX) from Peritoneal
Metastasis of Colorectal Cancer (PmCRC) for Improved
Prediction of Therapy Response
Mathias Dahlmann 1, 2; Beate Rau 3; Bernadette Brzezicha 4; Britta Büttner 4;
Eva Pachmayr 3; Oliver Popp 5; Philipp Mertins 5; Ulrich Keilholz 6;
Wolfgang Walther 1, 4; Ulrike Stein 1, 2
1Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin
and Max-Delbrück-Centrum für Molekulare Medizin, Translationale Onkologie
solider Tumore, Berlin, Deutschland
2Deutsches Krebsforschungszentrum, Deutsches Konsortium für Translationale
Krebsforschung, Heidelberg, Deutschland
3Charité – Universitätsmedizin Berlin, Chirurgische Klinik, Berlin, Deutschland
4EPO - Experimental Pharmacology and Oncology GmbH Berlin-Buch, Berlin,
Deutschland
5Max-Delbrück-Centrum für Molekulare Medizin and Berlin Institute of Health,
Proteomics Technology Platform, Berlin, Deutschland
6Charité – Universitätsmedizin Berlin, Comprehensive Cancer Center Charité,
Berlin, Deutschland
Purpose: For patients with colorectal cancer (CRC) peritoneal metastasis
(pm) represents a terminal tumor stage with limited therapeutic options.
Appropriate patient-derived xenogra (PDX) models of this disease allow
preclinical trials to evaluate predictive biomarker signatures for standard
chemotherapeutics, but also to nd novel therapeutic targets and treat-
ment options. is approach of personalized oncology might increase
therapeutic ecacy and overall survival of pmCRC patients.
Methods: For model establishment, surgical specimens were transplanted
subcutaneously (s.c.) onto immunocompromized NSG mice and engra-
ed tumors were transferred to NMRI nu/nu mice for further passaging.
Models were characterized by histopathology, immunohistochemistry
and molecularly characterized by RNAseq and (phospho-) proteomics.
Chemosensitivity of pmCRC models was evaluated on a panel of conven-
tional chemotherapeutic and targeted drugs. Bioinformatics of molecular
data of patient and patient-derived tissue was used to evaluate predictive
signatures for single drug treatments, but also to retrace mechanisms for
response or resistance of individual models.
Results: e drug testing revealed individual response patterns in PDX.
Most interestingly, dierent drug response patterns were observed in
models derived from mucinous vs. non-mucinous tumor tissue, but also
originating from the omentum or peritoneum of the same patient. Dier-
entially expressed genes of responding and non-responding models were
determined for most of the applied standard chemotherapeutics, whereas
idiosyncratic eects of individual therapy responses for targeted drugs
could be molecularly retraced.
Conclusions: We successfully established a platform of preclinical models
for pmCRC. Patient-derived models maintain basic characteristics such
as the morphology of the patient tumor in early passages, reect het-
erogeneous response rates, and can be used to evaluate novel predictive
biomarker signatures and therapeutic targets for improved personalized
precision oncology.
799
A Metastatic MACC1WNT/Β-Catenin-S100A4 Axis Promotes
Cancer Cell Motility in CRC
Benedikt Kortüm 1; Harikrishnan Radhakrishnan 1; Fabian Zincke 1;
Christoph Sachse 2; Dennis Kobelt 1; Mathias Dahlmann 1; Ulrike Stein 1
1Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin
& Max-Delbrück-Center for Molecular Medicine, Berlin, Deutschland
2NMI-TT Pharmaservices, NMI Technologietransfer GmbH, Berlin, Deutschland
Purpose: Colorectal Cancer (CRC) is a leading cause of death worldwide,
mainly due to metastatic spread. Biomarkers allow identication of high
risk patients and expose targetable vulnerabilities of CRC. Metastasis-As-
sociated in Colon Cancer-1 (MACC1) predicts metachronous metasta-
ses and promotes cell motility and metastasis. Wnt/β-catenin signaling is
commonly deregulated in CRC and its target genes such as the metasta-
sis-associated gene S100A4 induce and cell motility and motility. In this
study we expose a functional link between both prometastatic genes in
CRC progression.
Methods: MACC1 and S100A4 expression were analyzed in CRC cohorts
as well as in CRC cell lines. Following overexpression or CRISPR-mediat-
ed knockout of MACC1 Wnt signaling was assessed with TOPash assays.
S100A4 regulation was quantied with a promoter reporter assay and on
mRNA and protein level. Cancer cell migration was examined in Boyden
chambers. e MACC1-Wnt/β-catenin-S100A4 axis was intercepted with
siRNA against β-catenin and Wnt inhibitors. Phosphorylation of β-caten-
in was assessed with DigiWest and Western blot.
Results: MACC1 enhances Wnt/β-catenin activity in CRC cells and upreg-
ulates S100A4 expression and S100A4 promotor activity. Knockdown of
β-catenin and Wnt inhibitors revert the upregulation of S100A4. MACC1
overexpression increases transwell migration in S100A4-procient CRC
cells, but not in S100A4-knockout cells. Mechanistically, MACC1 stabi-
lizes β-catenin post-transcriptionally through phosphorylation of serine
552. Further, the mRNA expression of MACC1 and S100A4 correlates
positively in two independent CRC patient cohorts.
Conclusions: MACC1 upregulates S100A4 via Wnt/β-catenin signaling
and drives CRC cell motility in a S100A4-dependent manner. S100A4 is
the eector of MACC1-driven cell motility in CRC. Depletion of S100A4
with neutralizing antibodies and small-molecule inhibitors will be tested
against MACC1-driven CRC.
Disclosure Statement: No conict of interest to declare.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 203
Inhalt
2018
Index
2018
846
Targeted Chemotherapy Using VLP and Hydrogel
Jochen Gaedcke 1; Azadeh Azizian 1; Jens Gruber 2; Michael Ghadimi 1
1University Medical Center Göttingen, Department of General, Visceral and
Pediatric Surgery, Göttingen, Deutschland
2Deutsches Primatenzentrum DPZ, Primatengenetik, Göttingen, Deutschland
Purpose: Most eective chemotherapeutics show a number of side eects
due to the fact, that they damage both, cancer cells and non-cancer cells.
erefore, there is an immense need for targeted therapy options. Virus
like particles (VLPs) are a candidate delivery system for therapeutics.
With the aid of VLPs we aimed to apply a non-targeted therapy (Oxal-
iplatin and Paclitaxel) in a targeted way. Furthermore, we investigated the
usefulness of hydrogel techniques for a continuous application.
Methods: In this study, we treated ve cell lines of dierent entities (SKBR-
3, SW480, SW620, L3.6, PaTu-8988T) with Oxaliplatin and Paclitaxel in
four groups: A) we added Oxaliplatin (250µM) or Paclitaxel (100µM) to
the medium (as positive control). B) We added VLPs, which were dialyzed
with Oxaliplatin or Paclitaxel overnight. C) We treated the cells with hy-
drogel containing Oxaliplatin or Paclitaxel respectively, and D) we treated
the cells with hydrogel containing VLPs, which were dialyzed with Oxal-
iplatin or Paclitaxel overnight. We performed Cell titer Blue (CTB) for cell
viability measurement aer 7/14/21 days (n=3).
Results: CTB assays show a signicant decrease of cell viability applying
Paclitaxel containing VLPs (16% cell viability aer 7 days in SKBR-3, 15%
in SW480, 16% in SW620, 10% in L3.6 and 6% in Patu-8988T), whereas
Oxaliplatin does not accumulate well in VLPs due to its molecular weight.
Applying hydrogel shows a continuous eect even aer 21 days.
Conclusions: Applying chemotherapy via VLPs oers an opportunity to
minimize side eects and enhance the antitumor-eect. However, not all
therapeutics can be accumulated in VLPs. e hydrogel technique oers a
continuous application of chemotherapy with a high local eciency. Both
methods can be combined to achieve an eective and targeted therapy.
849
Diagnostic Leukapheresis as a Liquid Biopsy to Collect
Circulating Tumor Cells in Breast Cancer Patients – Clinical
Safety
Franziska Meier-Stiegen 1; Bernadette Jäger 1; Florian Reinhardt 1;
Johanna Naskou 1; André Franken 1; Hans Neubauer 1; Christiane Driemel 2;
Eugen Ruckhäberle 1; Dieter Niederacher 1; Johannes Fischer 3;
Nikolas H. Stoecklein 2; Tanja Fehm 1
1University Hospital Düsseldorf, Gynecology and Obstetrics
2University Hospital Düsseldorf, Department of General, Visceral and Pediatric
Surgery
3University Hospital Düsseldorf, Institute for Transplantation Diagnostics and
Cell Therapeutics
Purpose: e prognostic relevance of CTCs has been shown for all set-
tings of breast cancer. e low number of CTCs detected by established
methods limits the possibility for further evaluation. Implementation of
diagnostic leukapheresis (DLA) enables detection of CTCs at high fre-
quency. e aim of this clinical study was to assess the safety of DLA in 39
patients with primary and metastatic breast cancer.
Methods: DLA was performed at least 1d before surgery or chemothera-
py. Complete blood count as well as measuring blood pressure and heart
rate was performed before and aer DLA. CTCs in DLA products were
enumerated using CellSearch.
Results: In 2/41 patients DLA could not be performed due to technical
problems. 26 patients had non metastatic breast cancer. 13 patients were
diagnosed with MBC. Severe adverse events resulting in interruption
of apheresis were not observed. DLA did not interfere with the start of
chemotherapy or surgery. Complete blood count before and aer DLA
showed statistic signicant but clinically irrelevant decrease in numbers of
leukocytes, thrombocytes, hemoglobin and the percentage of hematocrit.
11/21 DLA samples (52%) of patients with primary breast cancer con-
tained CTCs (1 - 51). 11/13 DLA samples (85%) of patients with MBC
contained CTCs (1 - 2913).
Conclusions: Establishing a routine DLA protocol we demonstrated that
this procedure is clinically safe and can be implemented into the clinical
workow of breast cancer patient care.
853
Repositioned Drugs for Targeted Therapy of Biomarker Driven
Cancer Metastasis
Dennis Kobelt 1, 2; Juneja Manisha 1; Ulrike Sack 1; Daniel Perez-
Hernandez 3, 4; Fabian Zincke 1, 2; Bjoern Gohlke 5; Mathias Dahlmann 1, 2;
Juliane Maria Liebeskind 1; Preissner Robert 5; Von Kries Jens Peter 6;
Gunnar Dittmar 3, 4; Joe Lewis 7; Wolfgang Walther 1; Ulrike Stein 1, 2
1Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin,
and Max-Delbrück-Center for Molecular Medicine
2German Cancer Consortium (DKTK)
3Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association
4Luxembourg Institute of Health
5Charité Universitätsmedizin Berlin
6Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Heidelberg
7The European Molecular Biology Laboratory (EMBL), Berlin
Purpose: Biomarkers are important tools to stratify patients for their can-
cer and metastasis risk. MACC1 and S100A4 are drivers and prognostic
biomarker for cancer progression and metastasis in a large variety of solid
tumor types, particularly colorectal cancer. Patients expressing both bio-
markers have the worst prognosis. erefore, we are aiming to target both
biomarkers simultaneously.
Methods: We used two independent luciferase reporter based high
throughput screenings (HTS) comprising over 34000 compounds of four
dierent compound libraries. Similarly, the LOPAC library was screened
for S100A4 inhibitors. Most promising compounds were characterized in
vitro using qRT PCR, Western Blot, EMSA, cell viability and motility as-
says. For MACC1 possible drug–target docking was shown in silico. To
analyze the dependence of MACC1 on post-translational modications
Mass spectrometry and mutant forms of MACC1 were used additionally.
We demonstrated the in vivo drug eects by bioluminescence imaging of
xenograed mice. Patient samples were analyzed by qRT PCR.
Results: Two independent HTS revealed a statin as most potent MACC1
transcriptional inhibitor. ey remarkably inhibited MACC1 promoter
activity and expression resulting in reduced cell motility. Statins impair
the binding of the transcriptions factors c-Jun and Sp1 to the MACC1
promoter. In CRC-xenograed mice, it restricted MACC1 expression and
liver metastasis. MACC1 gets phosphorylated by MEK1. e phosphory-
lation of MACC1 by MEK1 is necessary for the MACC1 induced pheno-
type. Niclosamide was identied as most potent inhibitor for S100A4 gene
expression. It lowered cell motility in vitro and metastasis formation in
vivo. Targeting both biomarkers synergistically reduced cellular motility
and proliferation.
Conclusions: is is the rst identication of inhibitor combinations re-
stricting cancer progression and metastasis via the biomarkers MACC1
and S100A4. is drug repositioning might be of therapeutic value for
CRC patients stratied for expression of both MACC1 and S100A4.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts204
Inhalt
2018
Index
2018
Other Topics
Best-of-Abstracts-Vorträge
274
Durability of Response with Larotrectinib in Adult and
Pediatric Patients with TRK Fusion Cancer
Serge Leyvraz 1; David M. Hyman 2; Cornelis M. van Tilburg 3;
Catherine M. Albert 4; Daniel Sw. Tan 5; Birgit Geoerger 6; Anna F. Farago 7;
Theodore W. Laetsch 8; Shivaani Kummar 9; François Doz 10; Ulrik Lassen 11;
Steven G. Dubois 12; Ray Mcdermott 13; Leo Mascarenhas 14; Jordan Berlin 15;
Erin R. Rudzinski 16; Michael C. Cox 17; Shivani Nanda 18; Barrett H. Childs 18;
Alexander Drilon 2; David S. Hong 19
1Charité Comprehensive Cancer Center, Charité Berlin, Berlin, Deutschland
2Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center,
New York, United States
3Hopp Childrens Cancer Center Heidelberg (KiTZ), Heidelberg University
Hospital and German Cancer Research Center (DKFZ), Heidelberg, Deutschland
4Fred Hutchinson Cancer Research Center, Seattle Children’s Hospital, University
of Washington, Seattle, United States
5National Cancer Centre Singapore, Singapore
6Gustave Roussy Cancer Center, Université Paris-Sud, Université Paris-Saclay,
Villejuif, Frankreich
7Massachusetts General Hospital Cancer Center, Boston, United States
8Southwestern Medical Center/Childrens Health, University of Texas, Dallas,
United States
9Stanford Cancer Institute, Stanford University, Palo Alto, United States
10Institut Curie, SIREDO Oncology Center (Care, Innovation and research for
children and AYA with cancer), Paris Descartes University, Paris, Frankreich
11Rigshospitalet, Copenhagen, Dänemark
12Dana-Farber/Boston Childrens Cancer and Blood Disorders Center, Boston,
United States
13St. Vincent’s University Hospital and Cancer Trials Ireland, Dublin, Ireland
14Childrens Hospital Los Angeles, University of Southern California Keck School
of Medicine, Los Angeles, United States
15Vanderbilt University, Nashville, United States
16Seattle Childrens Hospital and University of Washington Medical Center,
Seattle, United States
17Loxo Oncology, Inc., San Francisco, United States
18Bayer U.S. LLC, Whippany, United States
19The University of Texas MD Anderson Cancer Center, Houston, United States
Purpose: Genomic rearrangements involving NTRK1/2/3 result in consti-
tutively active TRK fusion proteins that are oncogenic drivers in multiple
cancers. Larotrectinib is a selective TRK inhibitor approved for the treat-
ment of any TRK fusion cancer based on a primary analysis in 55 pts from
3 clinical trials. We now report median duration of response (DOR) data
in this primary cohort, and updated data in an expanded cohort of 159
total TRK fusion pts treated with larotrectinib, with 153 (55 primary + 98
supplemental) evaluable for ecacy.
Methods: Patients with TRK fusion cancer detected by local molecular
proling were treated with larotrectinib across 3 studies (NCT02122913,
NCT02637687, NCT02576431). Disease status was assessed by using RE-
CIST1.1. Data cut-o was 19 Feb 2019.
Results: In the primary cohort of 55 pts with a median follow-up of 26
mo, the median DOR in 44 pts with complete or partial responses was
35.2 mo (95% CI 21.2–NE), with 17 progression events and 27 responses
ongoing (range 1.6 –44 mo). e median PFS in the primary cohort was
25.8 mo (95% CI 9.9–NE), with 27 pts having progressed. In the expanded
combined dataset, the most common tumor types included so tissue sar-
coma (n=36), infantile brosarcoma (n=29), thyroid carcinoma (n=26),
salivary gland carcinoma (n=21), and lung cancer (n=12). e median age
was 43 yrs, ranging from <1 mo to 84 yrs; 33% <18 yrs. e overall ORR
was 79% (95% CI 72–85), with complete responses in 16%. Adverse events
were primarily grade 1-2, with 13% of pts having had a grade 3-4 event
related to larotrectinib. Only one pt discontinued due to an AE related to
larotrectinib.
Conclusions: ese data conrm the tissue-agnostic ecacy and long
durability of response in pts with TRK fusion cancer treated with laro-
trectinib. Larotrectinib continued to demonstrate a favorable long-term
safety prole. Screening pts for NTRK gene fusions should be actively
considered.
© 2019 European Society for Medical Oncology, Inc. Reused with permission.
is abstract was accepted and previously presented at the 2019 ESMO Annual
Meeting. All rights reserved.
Disclosure Statements:
Serge Leyvraz reports personal fees from Immunocore, and Bayer outside the
submitted work.
David M. Hyman reports Consulting or Advisory Role: Chugai Pharma, CytomX
erapeutics, Boehringer Ingelheim, AstraZeneca, Pzer, Bayer, Genentech, and
Research Funding: AstraZeneca, Puma Biotechnology, Loxo, Bayer, Travel, Accom-
modations, Expenses: Genentech, Chugai Pharma.
Cornelis M. van Tilburg reports Bayer: advisor, and Novartis: advisor.
Catherine M. Albert none.
Daniel S.W. Tan reports Consultancy: Novartis, Merck, Loxo, AstraZeneca, Roche,
Pzer, Travel: Pzer, Boehringer Ingelheim, Roche, Honoraria: BMS, Takeda,
Novartis, Roche, Pzer, and Research funding: Novartis, GSK, AstraZeneca.
Birgit Geoerger none.
Anna F. Farago reports Research support ‒ Bayer Healthcare, Loxo Oncology,
Inc., Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, PharmaMar,
Merck, Ignyta, Amgen, Novartis, Consultant ‒ Bayer Healthcare, Loxo Oncology,
Inc., Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, PharmaMar,
Boehringer Ingelheim, and Honorarium – DAVA Oncology, Clinical Care Options,
Medical Learning.
eodore W. Laetsch reports Consultancy: Novartis, Bayer, Loxo, Lilly, and
Research funding: Pzer, Novartis, Bayer, Loxo, Abbvie, Amgen, Atara, Biother-
apeutics, BMS, Lilly, Epizyme, GSK, Janssen, Jubilant Pharmaceuticals, Novella
Clinical, Servier.
Shivaani Kummar reports Bayer: advisory board, honoraria, travel support.
François Doz reports BAYER: travel expenses, advisory board, and ROCHE:
advisory board.
Ulrik Lassen reports Bayer advisory board.
Steven G. DuBois reports Loxo: consultancy and travel expenses, and Roche:
travel expenses.
Ray McDermott reports Travel expenses: Janssen-Cilag, Pzer, Honoraria: Bayer,
Sano, Janssen, Astellas, BMS, MSD, Pzer, Novartis, Clovis, and Research fund-
ing: Sano, Janssen, Bayer, Astellas.
Leo Mascarenhas reports Bayer: speaker bureau.
Jordan Berlin reports Research funding: PsiOxus, Bayer, EMD Serono, Sympho-
gen, Roche/Genentech, Immunomed, Honoraria, Nestle, and Consulting/advisory,
Rafeal, Seattle Genetics, EMD Serono, Bayer, eisai, Taiho, Armo,Gritstone, Astra
Zeneca, Celgene, Erytech.
Erin R. Rudzinski wird nachgereicht.
Michael C. Cox was an employee of Loxo Oncology Inc.
Shivani Nanda is an employee of Bayer.
Barrett H. Childs is an employee of Bayer.
Alexander Drilon reports HONORARIA/ADVISORY BOARDS: Ignyta/Ge-
nentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP erapeutics,
AstraZeneca, Pzer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui
erapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, ASSOCIATED
RESEARCH PAID TO INSTITUTION: Pzer, Exelixis, GlaxoSmithKlein, Teva,
Taiho, PharmaMar, RESEARCH: Foundation Medicine, ROYALTIES: Wolters
Kluwer, OTHER: Merck - Food/Beverage, Puma - Food/Beverage, and CME
HONORARIA: Medscape, OncLive, PeerVoice, Physicians Education Resources,
Targeted Oncology, Research to Practice.
David S. Hong reports Research/Grant Funding: AbbVie, Adaptimmune, Amgen,
Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate erapeutics, Genentech,
Genmab, Ignyta, Innity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati,
MiRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pzer, Seattle
Genetics, Takeda, Travel, Accommodations, Expenses: LOXO, MiRNA, ASCO,
AACR, SITC, Genmab, Consulting or Advisory Role: Alpha Insights, Axiom,
Adaptimmune, Baxter, Bayer, Genentech, GLG, Group H, Guidepoint Global,
Innity, Janssen, Merrimack, Medscape, Numab, Pzer, Seattle Genetics, Takeda,
Trieza erapeutics, and Other ownership interests: Molecular Match (Advisor),
OncoResponse (founder), Presagia Inc (Advisor).
DKK_Abstracts_001-246.indd 204 11/02/20 12:05 PM
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 205
Inhalt
2018
Index
2018
Poster
44
Prähabilitation VOR Onkochirurgischen Eingrien
Carl Meißner; Karsten Ridwelski
Klinikum Magdeburg - Klinik für Allgemein- und Visceralchirurgie, Magdeburg,
Deutschland
Purpose: It has long been known that regular exercise protects against
chronic diseases, reduces the overall risk of mortality, and has enormous
potential for preventive medicine, especially with regard to the genesis of
tumors..
Methods: Literature review.
Results: e purpose of the following article is to give an overview of the
current status and preparation for major surgical operations.
Conclusions: Nutrition in the operative discipline makes sense. ere are
now appropriate guidelines.
322
Assessment of Treatment Options for Operated Patients with
Stage IIIA Non-Small Cell Lung Cancer (NSCLC) Based on
Baden-Württemberg Clinical Cancer Registry Data
Franziska Kanz 1; Julia Häberlin 1; Philipp Morakis 1; Johannes Englert 2
1Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg,
Geschäftsstelle Qualitätskonferenzen, Stuttgart, Deutschland
2Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg
Purpose: is analysis aimed at assessing whether cancer registry data
can be used to show dierent treatment options of NSCLC stage IIIA pa-
tients in the state of BW.
Methods: e analysis is based on data from BW Cancer Registry on di-
agnoses from 2014 to 2016. e data included UICC stage IIIA NSCLC
(ICD-10: C34) patients, based on cTNM (version 7 and 8), who received
anatomic or atypical resection aer being diagnosed. Neoadjuvant thera-
py was dened as a start of therapy within 7 to 14 weeks prior to resection,
adjuvant therapy was characterized by a start of therapy within 60 days
aer surgery. e data consists of reports from hospitals in BW and is
based on the ADT/GEKID-dataset.
Results: 1.038 stage IIIA NSCLC patients were included in the analysis.
Of those, 453 received surgical tumor resection, whereof 79% were pri-
mary resections. Another 13% (n=59) of the operated patients received
neoadjuvant therapy. Over time (year of diagnosis 2014 to 2016), the fre-
quency of neoadjuvant therapy increased from 8% to 20% whereas the
frequency of initially operated patients decreased from 84% in 2014 to
74% in 2016. From the primary resected patients, 39% were treated with
adjuvant therapy.
Conclusions: First evaluations with data from BW Cancer Registry on the
application of dierent oncological treatment strategies are feasible. e
analysis of various treatment modalities in the clinical practice is partic-
ulary vital for heterogeneous groups of tumor patients such as stage IIIA
NSCLC patients. With further improvement of data quality and timeline-
ness of data in the upcoming years, advanced analyses – also to show the
application of new therapy strategies – can be realized.
379
Prevalence of Dietary Supplement Use in Patients with Cancer
Maja Tank 1; Lindsey Otten 2; Nicole Stobäus 2; Jörg Heßling 3;
Kristina Franz 2; Kristina Norman 2
1MVZ Tempelhof Onkologie, Praxis, Berlin, Deutschland
2Forschungsgruppe Ernährung und Körperzusammensetzung; Klinik für
Geriatrie und Altersmedizin, Charité – Universitätsmedizin Berlin, corporate
member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin
Institute of Health, Berlin, Germany, Berlin, Deutschland
3Onkologie am Segeliegerdamm, Praxis, Berlin, Deutschland
Purpose: e use of dietary supplements (DS) such as phytopharmaceu-
ticals, trace elements and vitamins represents a rapidly growing market. It
is oen believed that DS from natural sources are harmless, non-toxic and
health-supporting. However, use of DS is frequently not reported to doc-
tors (1), although evidence regarding negative interactions between DS
and cancer treatment is increasing (2). is survey investigated prevalence
of DS use in patients with cancer.
Methods: We conducted a survey in 756 outpatients (aged 70.4±11.9)
undergoing cancer treatment, using a self-administered questionnaire
about frequency of intake, type of DS, changes in dietary habits, source of
information and motivation for DS use.
Results: 49.3% of patients reported current intake of DS, with a higher frequen-
cy in women (53.7 vs. 44.9%, p<0.001). 39.4% started intake of DS and 47.2%
changed their dietary habits upon cancer diagnosis. Patients listed oncologists
(32.3%), GP´s (30.7%) and print media (29.9%) as source of information. Only
15.5% of patients received consultation by dietitians. Phytopharmaceuticals
(15.2%), calcium (14.4%), vitamin B complex (13.1%) and multivitamin supple-
mentation (11.5%) were the most frequently taken supplements. 28.3% of pa-
tients stated supporting the immune system as the main reason for taking DS.
Conclusions: Our data imply that a relevant proportion of patients take
DS and change their nutritional habits aer cancer diagnosis. Knowing
about the potential interactions between DS and anti-cancer treatment,
these results emphasize the need for assessment of DS, and phytopharma-
ceuticals in particular.
References:
1. JAMA Network Open. 2018;1(7): Levy A G et al
2. ASCO educational Book. 2014; e478: Harvie, M
Disclosure Statement: e authors declare no conict of interest.
434
Ultrasound Guided Biopsy of Lymph Nodes
Thorsten Nitsch; Thomas Südho
II. Med Klinik, Klinikum Passau, Passau, Deutschland
Purpose: Enlarged lymph nodes are oen in malignant diseases, espe-
cially lymphoma. A reliable histology is the backbone to plan therapy.
e gold standard to get a reliable histology particularly in lymphoma is
the surgical excision. But a excision is invasive and need resources. Ultra-
sound is an easy and broadly available procedure also for a guided biopsy.
Here we report about target regions, ecacy and rate of complications.
Methods: is is a retrospective analysis of ultrasound g. biopsies in our
division. Device: Toshiba Aplio 400. According to localization we used a
convex array transducer, with biopsy application or a linear array trans-
ducer, with “free hand” technique. We applied True-cut needles with a
range from 14 to 18G. e b. were done under local anesthesia and aseptic
conditions. From each localization we obtained three b. on average and a
cytology. Complications were graded in three categories: 1 for minor up
to 3 for severe c..
Results: 1276 biopsies in dierent organs, therefrom 402 (31%) are lymph
nodes. Results of this lymph node b.: 45% carcinoma, 39% lymphoma,
14% non- malignant and 2% no reliable histo.. Lymphoma subdivision:
54% high malignant NHL, 42% low mal. NHL and 4% Hodgkin-L.
Locations: neck: 40,6%, groin 20%, axilla: 18%, abdomen: 11%, retroperi-
toneum: 6%, iliacal: 2%, mediastinum 1%, miscellaneous: 0,4%.
Reliable histology: 98%, no need of further interventions.
Complications: 3%. Mostly minor c. like short pain.
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Conclusions: Our analysis shows that ultrasound g. biopsy achieved a re-
liable histology in 98% with no need of further interventions. Complica-
tions occurred in 3% (mostly minor c. like short pain). us we conclude
that surgical excision is maybe not the gold standard for the rst line and
should be reserved for the cases of uncertain histology. Our result could
be base for a prospective randomized study: surgical excision versus ultra-
sound guided biopsy in lymph nodes.
Reference:
1. Nitsch T., Suedho T. Ultraschall gesteuerte Lymphknotenbiopsie. DLT 2019.
J.Ultraschall i.d.Med.. In press
Disclosure Statement: No conict of interest.
457
Shared Decision-Making in Cancer Care: Ongoing Process
Evaluation of a Stepped Wedge Cluster Randomized
Implementation Trial
Isabelle Scholl; Anja Lindig; Wiebke Frerichs; Pola Hahlweg
Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum
Hamburg-Eppendorf, Hamburg, Deutschland
Purpose: Shared decision-making (SDM) is highly relevant in oncology,
demanded by patients and prioritized by health policies. However, rou-
tine implementation continues to lag. Implementation science stresses
the importance of a thorough process evaluation when conducting im-
plementation studies. e aim of this study is to evaluate the process of
a multicomponent implementation program designed to foster SDM in
routine cancer care.
Methods: e stepped wedge implementation study is conducted in three
cancer care departments. It consists of training and coaching of clinicians,
patient activation, provision of information material and decision aids,
revision of quality management documents, and reection of current or-
ganization of tumor boards. We conducted a mixed methods process eval-
uation, including interviews with recipients, eld notes, and documenta-
tion of actual delivery of implementation strategies in each clinic, giving
insights into reach and delity of implementation.
Results: We concluded the second of three implementation phases. We
trained 50% of eligible clinicians. Facilitators included leadership support
and delivery of training during regular meeting slots. Barriers included
sta shortage and competing demands. 44% of clinicians participated in
individual coaching. Adaptations regarding dose and timing of delivery
were necessary. Information and patient activation material were distrib-
uted in all parts of the clinics. Revision of quality management documents
and reection of tumor boards progressed, but its implementation took
more time than expected. Results of process evaluation of the third and
nal implementation phase will be presented at the conference.
Conclusions: Process evaluation oers reliable insights into the realiza-
tion of a complex SDM implementation program in cancer care. Although
we were generally able to pursue the implementation strategies, adapta-
tions to the study protocol were necessary. Outcome evaluation will reveal
whether reach was sucient to foster SDM implementation.
465
Translation, Adaption and Psychometric Testing of the
German Version of the Organizational Readiness for
Implementing Change Measure (ORIC)
Anja Lindig; Pola Hahlweg; Eva Christalle; Isabelle Scholl
Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum
Hamburg-Eppendorf, Hamburg, Deutschland
Purpose: For the successful implementation of shared decision-making
(SDM) in routine cancer care, organizational readiness for change might
be a crucial factor. e 10-item measure Organizational Readiness for
Implementing Change (ORIC) assesses change commitment and change
ecacy from the healthcare professionals’ (HCPs’) perspective. e ORIC
was not available in German yet. e aim of the study was to translate
the ORIC into German, adapt it for the context of SDM, and assess its
psychometric properties.
Methods: We translated the original English ORIC into German using a
team translation protocol. e translated version was revised according
to comprehensibility assessment via cognitive interviews with HCPs. For
psychometric evaluation we used data from a SDM implementation study.
Secondary analysis included analysis of acceptance (response rate), struc-
tural validity (exploratory factor analysis, conrmatory factor analysis),
item characteristics (item diculties, corrected item-total correlations,
inter-item correlations), and reliability (Cronbachs α).
Results: We analyzed n=11 cognitive interviews and n=230 question-
naires. Translation and adaption of the ORIC was successful except for
item 10, which showed low comprehensibility. Response rate was > 97%.
Structural validity analysis provided a one factorial structure. Item di-
culties ranged between 55.98 and 65.32, corrected item-total-correlation
ranged between .66 and .74, inter-item correlations ranged between .43
and .72, and Cronbachs α was .93.
Conclusions: is study provides the rst German ORIC, a brief and
highly accepted measure with satisfying psychometric properties. To in-
crease comprehensibility of the measure we suggest removing item 10.
e German ORIC can be used to analyze organizational readiness for
change as a precursor for implementation success in routine cancer care
in German-speaking countries.
490
Patient’s Expertship Improves Medical Demand Research – A
Cooperation with the German Federal Association of Throat
Cancer Patients
Stefanie Walter 1, Philipp Steinau 2, Christian Keinki 3, Jutta Hübner 3,
Jens Büntzel 2
1Bundesverband der Kehlkopfoperierten, Bonn, Deutschland
2Klinik für HNO-Erkrankungen, Kopf-Hals-Chirurgie, Südharz-Klinikum
Nordhausen gGmbH, Nordhausen
3Medizinische Klinik II, Universitätsklinikum Jena, Jena, Deutschland
Purpose: Medical demand research has to integrate the view of the rel-
evant patient groups. How is it possible to use the expert knowledge of
patients for this questionnaire-research?
Methods: Two interview studies were started together with the German
Federal Association of roat Cancer Patients. We used a three step algo-
rithm for developing the questionnaires: 1. Narrative interviews with 3-4
patients about the specic topic (project 1: Loss os smell aer laryngectomy,
project 2: interests in articial intelligence). 2. Developing prototypes of
questionnaire together with the interview patients , and 3. Pilot interviews
with one self-help group and lingual adaption / correction of the ques-
tionnaires.
Results: e nalized questionnaires were distributed according the
population data of German federal states via the (federal state) self-help
groups. e questionnaire and the letter of introduction were sent along
with a stamped addressed envelope for the return of the questionnaire.
198/293 patients answered in the medical project 1 (67.6%). e ques-
tionnaire about artical integlligence was lled out by 151/293 patients
(51.5%). Both representive data pools are used by medical sta as well as
patient interest groups. Patient’s answers for both questionnaires will be
avaiable in detail at the congress.
Conclusions: Integration of patient’s expertship improves the quality and
acceptance of questionnaires in medical demand research..
Disclosure Statement: e authors disclose any conict of interest.
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557
Undergraduate Medical Education in Radiation Oncology:
A Student‘s Perspective
Sarah Knödler 1, Kathrin Gennen 2, Thorben Hölscher 3, Lukas Käsmann 2
1University Hospital Ulm, Department of Radiation Oncology, Ulm, Deutschland
2University Hospital, LMU Munich, Department of Radiation Oncology, Munich,
Deutschland
3University Hospital Köln, Department of Radiation Oncology, Köln,
Deutschland
Purpose: Radiation oncology is an integral part of the medical studies
curriculum in Germany. However, the specialization is taught dierently
in medical schools. We aimed to provide a dierentiated view about teach-
ing methods used in German medical schools in order to give recommen-
dations and actively integrate medical students into research and clinical
practise.in the eld of radiation oncology.
Methods: An online survey containing 10 questions was sent to 40 mem-
bers of the German society of radiation oncology (DEGRO e.V.) students
working group (Club100). A questionnaire of students who are not mem-
bers of the working group but registered at the same university was in-
cluded for each completed questionnaire (matched pair design).
Results: 18 questionnaires were completed by student members of “Club
100” (responsive rate: 45%) and analyzed for congruence to responses of
the same university. All students were in the clinical part of their studies
at the time of the survey. 36% of the respondents reported that radiation
oncology was taught exclusively during the 3rd year of their study. 40%
indicated that radiation oncology was taught over several semesters (5th
– 10th). 100% of the students stated the subject was taught via classical
lecture-style teaching. 20% of all respondents had to attend a compulsory
clinical rotation during their study program. 100% of the lecturers were
oering clinical electives in their department. 44% of the students stat-
ed the possibility of attending an optional course in radiation oncology,
60% of all respondents reported that the completion of a doctoral thesis
in radiation oncology was actively promoted. 33% of the students indicat-
ed that the discipline was taught in an integrative manner during other
courses.
Conclusions: Radiation oncology is taught in classic lecture-style teach-
ing. Several medical schools integrate radiation oncology during other
courses. Lecturers need to evaluate optimal knowledge transfer and prac-
tise-orientated training methods in order to actively involve medical stu-
dents into the eld of radiation oncology.
560
Implementation of a Culture-Sensitive Training Course for
Volunteering in Hospice Care
Ferya Banaz-Yasar; Ulrike Ritterbusch; Karin Scheer
Hospizarbeit am Universitätsklinikum Essen, Westdeutsches Tumorzentrum,
Essen, Deutschland
Purpose: Hospice care aims the support of patients and their relatives in
advanced state of illness and at the end of life. It is important to preserve
their quality of life. Hospice care provides to support emotional, social,
and spiritual needs independent of cultural/religious aliation or ethnic
origin. Volunteers are very important in hospice care. ey work with pa-
tients and families, and also with caregivers and physicians. At University
Hospital Essen patients from all over the world are medicated. Research
shows a poor access to end-of-life care for ethnic minorities (Jansky, 2013).
e aim of this study is to learn more about the dierent and similar
attitudes of volunteers taking our culture-sensive course, to establish a
curriculum based culture-sensitive volunteer training and nally to reach
better access to hospice care for more patients.
Methods: To recruid volunteers we started an advertisement in a
newspaper. Furthermore, we used social media (Facebook, Instagram)
to promote our project. To inform the potential volunteers we invited
to information-meetings. Aer face-to-face interviews we included 12
volunteers. Aer completing training, we interviewed them, and they
got a questionnaire to get more information about personal and spiritual
meanings.
Results: e age o the volunteers is between 30 – 60. Nearly 90% are
women. Nationalites are german, turkish, slovak and polish. e access to
hospice- and palliative care increases in ethnic minority families. e vol-
unteers communicate with patients in native language. Information about
the opportunities in hospice and palliative care could be provided better.
Conclusions: e culture-sensitive volunteer training allows a better ac-
cess to hospice and palliative care for all people and a better communica-
tion between patients, families and caregivers.
Reference:
1. Maximiliane Jansky & Friedemann Nauck (2013) Palliativ- und Hospizver-
sorgung von Menschen mit Migrationshintergrund. Aktueller Stand und
Handlungsempfehlungen für Hospiz- und Palliativversorger. Universitätsme-
dizin Göttingen
573
Development and Evaluation of a Patient Empowerment
Intervention to Support Shared Decision-Making in Cancer
Care
Anja Lindig; Pola Hahlweg; Wiebke Frerichs; Isabelle Scholl
Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum
Hamburg-Eppendorf, Hamburg, Deutschland
Purpose: Many cancer patients want active engagement in treatment
decision-making. Interventions like Ask 3 Questions (A3Q) encourage
patients to ask questions during clinical encounters and strengthen their
abilities to engage in decision-making processes. A3Q was developed in
Australia and dierent versions of the A3Q intervention were used in im-
plementation programs around the globe. So far, A3Q was not available
in German. Aims of this study were to develop a German version of the
intervention and to assess its feasibility and acceptance in German routine
cancer care.
Methods: Dierent English versions of the A3Q intervention were trans-
lated into German following a team translation protocol. Comprehensi-
bility and relevance were tested via cognitive interviews with n=10 cancer
patients. Acceptance and feasibility were assessed in focus groups and in-
terviews with cancer patients, physicians and nurses. Focus groups and
interviews were analyzed using qualitative content analysis.
Results: In cognitive interviews, cancer patients of dierent age (49.0
years ± 11.27), gender (f=5, m=5), years with disease (4.8 years ± 3.55),
and health literacy levels participated. Comparison and testing of dierent
A3Q versions led to a revised version that was well understood and seen
as relevant for cancer patients. We conducted focus groups and interviews
with n=24 cancer patients of dierent cancer entities, n=17 nurses and
n=7 physicians. A3Q was perceived as a helpful tool to encourage patients
to ask more questions in clinical encounters. It was also seen as a guideline
for physicians in supporting to remember to answer important questions.
Barriers and facilitators of the use of A3Q in routine care will be presented
at the conference.
Conclusions: is study provides a German version of the A3Q interven-
tion. Preliminary results suggest that A3Q could be a helpful instrument
to empower patients to play an active role in decision-making processes.
Barriers and facilitators must be analyzed carefully to understand how to
best implement the A3Q intervention in German routine care.
587
How to Make Multidisciplinary Team Meetings in Cancer Care
More Patient-Centered? Recommendations from a Narrative
Review
Pola Hahlweg; Isabelle Scholl
Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum
Hamburg-Eppendorf, Hamburg, Deutschland
Purpose: Multidisciplinary team meetings (MDTMs, also called tumor
boards) are considered best practice in cancer care. However, MDTMs
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have been found to mostly discuss medical information and pay little at-
tention to the patient’s perspective and psychosocial situation. Hence, the
current organization of MDTMs has been argued to not support patient
centered-care (PCC) and shared decision-making (SDM) between phy-
sicians and patients. is review aimed to identify recommendations for
MDTMs to become more patient-centered.
Methods: A narrative review of existing literature recommending strate-
gies to foster interdisciplinary communication and patient-centeredness
in MDTMs was conducted. Two researchers with ample experience in
SDM research in cancer care including observational studies in MDTMs
reviewed the literature. Extracted recommendations were discussed with
clinical cooperation partners at a comprehensive cancer center in Ger-
many.
Results: We extracted recommendations from 30 publications, which in-
cluded original research and reviews as well as opinion pieces. is led to
13 recommendations regarding the following areas:
1) routine pathways and quality management standards (e.g., consis-
tent denomination as MDTM recommendation instead of decision);
2) participants (e.g., discussion of a case only if at least one participant
has met the patient);
3) information discussed during MDTMs (e.g., documentation of
more than one possible treatment, if uncertainty exists during meet-
ing);
4) tasks of the MDTM chair (e.g., communication and leadership train-
ing for MDTM chairs).
Aer discussion with clinical cooperation partners, changes in the setting
emerged as a h area (e.g., u-shaped seating arrangement).
Conclusions: Since MDTMs in their current organization do not foster
PCC and SDM, recommendations for changes towards more PCC and
SDM in MDTMs were reviewed and consolidated. ose recommenda-
tions can be used to inform implementation eort to foster patient-cen-
tered MDTMs and SDM in cancer care.
642
Implementation of an Interprofessional Counseling Program
for Complementary and Integrative Health Care at CCCS in
Baden-Wuerttemberg (CCC – Integrativ)
Stefanie Joos 1; Jan Valentini 1; Regina Stolz 1; Laura Bertram 1;
Nadja Klafke 2; Peter Martus 3; Katrin Tomaschko 4; Claudia Witte 5;
Markus Horneber 6; Cornelia Mahler 7
1Institute of General Practice and Multi-Disciplinary Healthcare , University
Hospital and Faculty of Medicine Tuebingen, Tübingen, Deutschland
2Department of General Practice and Health Services Research, University
Hospital Heidelberg, Marsilius-Arkaden, Heidelberg, Deutschland
3Institute for Clinical Epidemiology and Applied Biometry, Tübingen,
Deutschland
4AOK Baden-Wuerttemberg Hauptverwaltung, Fachbereich Integriertes
Leistungsmanagement, Stuttgart, Deutschland
5aQua Institute for Applied Quality Improvement and Research in Health Care,
Goettingen, Deutschland
6Department of Internal Medicine, Division of Oncology and Hematology,
Paracelsus Medical University Klinikum Nuernberg, Nürnberg, Deutschland
7Department of Nursing Science, University Tuebingen, Tübingen, Deutschland
Purpose: Up to 80% of all cancer patients want complementary and
integrative health care approaches (CIH) be part of their treatment.
Positive eects have been proven for some CIH procedures such as
yoga, acupuncture and herbal drugs. However, risks are also associated
with CIH procedures e.g. drug interactions. Within a clinical trial an
interprofessional, evidence-based CIH counselling program will be
established at four CCCs in Baden-Wuerttemberg.
Methods: Aim is to empower patients during the rst 6 months aer di-
agnosis and to advise them on chances and risks of CIH. Counselling is
oered by interprofessional teams of specially trained doctors and nurses
accompanied by intersectoral activities.Within a controlled, non-ran-
domized implementation study 2,000 patients (n=500 per CCC) will be
included in the intervention group and receive CIH counselling (min. 3
contacts within 3 months). Primary outcome is the PAM-13, a predictor
of patient activation. PAM-13 and secondary outcomes (e.g. quality of life,
self-ecacy, clinical parameters) will be measured at baseline (T1), aer 3
months (T2) and 6 months follow-up (T3). Data collection of the control
group (n=500) will start prior to the intervention using identical instru-
ments for primary/secondary outcomes at T1, T2, T3. Health insurance
data will be analyzed to evaluate the use of health care services. Process
evaluation will be conducted to identify relevant barriers and enablers for
later implementation.
Results: e study design will be presented.
Discussion: e results will provide relevant information for future com-
prehensive and evidence-based CIH roll-out.
Funded by the Innovationsfonds of the Federal Joint Committee 2019-2022.
700
Titel Clone: Clinical Trials in Oncology in the New Era of
OMICS, Big Data, and Modeling. A BMBF Funded Summer
School of the Krukenberg Cancer Center Halle (KKH) in
Systems Medicine
Susann Schulze 1; Eva Johanna Kantelhardt 2, 3; Haifa Kathrin Al-Ali 1
1Krukenberg Cancer Center Halle (Saale), Martin-Luther-University Halle-
Wittenberg/ University Hospital of Halle (Saale), Halle (Saale), Deutschland
2Institute of Medical Epidemiology, Biometrics and Informatics, Martin-Luther-
University Halle-Wittenberg, Halle (Saale), Deutschland
3Department of Gynecology, University Hospital of Halle (Saale), Halle (Saale),
Deutschland
Purpose: Innovative data in cancer biology and bioinformatics are revolu-
tionizing the understanding of cancer and have profound implications on
the design of clinical trials with novel ethical and legal challenges. BMBF
funded Summer Schools could be a platform facilitating interdisciplinary
knowledge transmission from research to healthcare.
Methods: CLONE (a ve-days program) was planned to bring physicians
and researchers from various disciplines in Systems Medicine together to
illuminate personalized oncology. e proposal of the KKH was accepted
within the BMBF e:Med Summer school grant in September 2018. Partic-
ipants from Germany and abroad were competitively selected by a panel
of experts based on submitted abstracts. e faculty included thirty-eight
national and international experts in their elds.
Results: CLONE took place from 24-28 June 2019 in Halle (Saale). A total
of 23 participants from ve countries qualied. e following topics were
discussed: Day 1: Stratied versus personalized cancer medicine; emerg-
ing developments in Omics and Big Data Analytics in Life Sciences. Day
2 (Omics): Genomics; Epigenetics; Proteomics. Day 3: (Big Data): Bioin-
formatics; Modeling and simulation; real world data including registries.
Day 4: (Clinical Trials in the era of Big Data): Planning and designing a
clinical trial; Preparing a trial; Science versus regulations. Day5 (Engaging
and communicating with patients): Ethical and legal considerations; Pa-
tients perspectives. ree poster walks and four workshops in molecular
pathology, proteomics, epidemiology and clinical trials were held. A daily
evening program was oered.
Conclusions: BMBF funding allowed a scientic exchange across dier-
ent disciplines relevant for cancer research and treatment. e need for
collaborative programs to analyse the vast amount of research data and
how to translate the results into prognostic biomarkers and tailored clini-
cal studies with targeted therapies were emphasized.
Disclosure Statement: Summer School was funded by BMBF. All authors have
nothing to declare.
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809
Cancer Drugs Aect the Interaction of Nanoparticles with an
in Vitro Placenta Barrier
Nicole Schwarze 1; Lennart Gresing 1; Angela Stelz 1; Christine Gräfe 1;
Silvio Dutz 2; Frank Wiekhorst 3; Andreas Hochhaus 1; Joachim Clement 1
1Abt. Hämatologie und Internistische Onkologie, Universitätsklinikum Jena,
Jena, Deutschland
2Institut für Biomedizinische Technik und Informatik (BMTI), TU Ilmenau,
Ilmenau, Deutschland
3Physikalisch-Technische Bundesanstalt, Berlin, Deutschland
Purpose: e incidence of cancer during pregnancy increases. In indus-
trialized countries women delay pregnancy to older ages, where the over-
all risk of cancer occurrence is elevated. Superparamagnetic iron oxide
nanoparticles (SPION) can serve as imaging contrast for magnetic reso-
nance imaging for early cancer detection in pregnant women. No harmful
potential for the developing fetus is expected. In this study we analyzed
the inuence of common cancer drugs on the behavior of SPIONs and a
model blood-placenta barrier.
Methods: A tri-culture model was used in a Transwell setting: Human
trophoblast representing placenta cells (BeWo) and pericytes (hPC-Pl)
formed the cellular barrier and reporter cells (MCF7 for doxorubicin
and paclitaxel and K-562 for imatinib) were place in the target compart-
ment. e cells were exposed to 0.002 mg/ml doxorubicin, 0.006 mg/ml
paclitaxel or 20 µM imatinib for 48h, and then 100 µg/cm2 neutral
starch-coated SPIONs were added for 24h. Barrier integrity was veried
by trans-endothelial resistance (TEER), molecular permeability and im-
munuorescence staining of tight junction protein ZO-1. e passage of
the therapeutic agents was evaluated via determination of the reporter
cells by ow cytometry (Annexin V APC/PI) or MTS assay. e distribu-
tion of SPIONs was evaluated by atomic absorption spectroscopy.
Results: Both, TEER and molecular permeability assay showed a neg-
ative inuence of doxorubicin and paclitaxel on blood-placenta barrier
integrity. No additional eects were observed by the presence of the neu-
tral-charged SPIONs. Doxorubicin markedly reduced ZO-1 expression
indicating loss of cell-cell contacts. Imatinib exhibited minor eects.
Doxorubicin and paclitaxel reduced the proportion of vital MCF7 to
44.4% ± 0.7% and 49.1 ± 2.5%, whereas imatinib reduced vitality of K-562
to 40% ± 4%. In the presence of the chemotherapeutics 1.5-fold more SPI-
ON can pass the in vitro barrier, but do not alter vitality of reporter cells.
Conclusions: erapeutic agents enable increased passage of SPIONs
through an in vitro blood-placenta barrier.
Late-Breaking Abstracts
Breast Cancer
Poster
962
Does Collagenase Treatment of Capsular Fibrosis Favor the
Spread of Triple Negative Breast Cancer Cells?
Katharina Marstaller1; Yannick Diehm2; Michael Zepp1;
Anna-Maria Seckler1; Martin Berger1; Sebastian Fischer2
1DKFZ, Arbeitsgruppe Toxikologie und Chemotherapie, Heidelberg,
Deutschland
2BG Klinik Ludwigshafen, Klinik für Hand-, Plastische- und Rekonstruktive
Chirurgie, Ludwigshafen, Deutschland
Purpose: CCH can be a valuable treatment option for capsular contrac-
ture aer silicone based breast reconstruction. e aim of this project was
to determine whether the treatment with the Collagenase bacterium his-
tolyticum (CCH) could be hazardous for patients with Triple- negative-
Breast-Cancer (TNBC) harboring residual tumor cells.
Methods: In order to determine the eect of CCH treatment on TNBC
cells we used human MDA-MB-231 TNBC cells in various in-vitro assays
including proliferation (MTT), cell cycle distribution (FACS) and apop-
tosis induction (FACS). In addition, MDA-MB-231 cells (1x10^6) trans-
fected with Firey-luciferase were used in a mouse model (NSG) to assess
the possible spread of the tumor cells in response to CCH treatment. An
orthotopic tumor was induced and monitored for 21 days using biolumi-
nescence imaging and caliper measurements.
Results: In the in-vitro experiments a signicant reduction of cell viabil-
ity was observed, as indicated by a 20% reduced proliferation of cells in
response to CCH treatment. is eect was caused by a slightly increased
incidence of apoptotic cells as conrmed by FACS analysis. Regarding the
cell cycle analysis, no signicant changes were observed. In vivo, the CCH
treatment at the dosage used caused no toxic side eects (skin perfora-
tion, bleeding). Most importantly, the monitoring of the tumor growth by
bioluminescence imaging and caliper measurements indicated no signs of
tumor spread in the treated animals.
Conclusions: CCH treatment shows no pro-metastatic eect on MDA-
MB-231 tumors but rather appears to inhibit cell-proliferation. us,
there is no indication of an increased risk for TNBC patients receiving
CCH treatment.
References:
Disclosure Statement: is study was sponsored by Endo Pharmaceuticals inc.
986
Predictors of Cardiorespiratory Fitness in Healthy and
Cancer-Diseased Women with a Germline BRCA1/2 Mutation
Participating in the Libre-1 Trial
Anika Berling-Ernst1; Maryam Yahiaoui-Doktor2; Marion Kiechle3;
Freerk Baumann4; Uwe Niederberger5; Michael Siniatchkin5;
Martin Halle1,6
1Department of Prevention, Rehabilitation and Sports Medicine, Technical
University of Munich (TUM), Munich, Deutschland
2Institute for Medical Informatics, Statistics and Epidemiology (IMISE) ,
University of Leipzig, Leipzig, Deutschland
3Department of Gynecology and Center for Hereditary Breast and Ovarian
Cancer, University Hospital rechts der Isar, Technical University of Munich (TUM),
Munich, Deutschland
4Department I of Internal Medicine, Center of Integrated Oncology Cologne
Bonn , University Hospital of Cologne, Cologne, Deutschland
5Institute of Medical Psychology and Medical Sociology, University Medical
Center Schleswig Holstein, Kiel, Deutschland
6DZHK (German Centre for Cardiovascular Research), partner site Munich Heart
Alliance, Munich, Deutschland
Purpose: BRCA1/2 mutation carriers are at an increased risk of develop-
ing breast and ovarian cancer compared to non-carriers. Studies indicate
that cardiorespiratory tness is an age-independent predictor of
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tumor-specic mortality in sporadic breast cancer survivors. e impact
of the cardiorespiratory tness on cancer prevention and prognosis in
BRCA1/2 mutation carriers is unknown. erefore, the purpose of the
study was to identify predictors of cardiorespiratory tness (VO2peak) in
healthy and cancer-diseased BRCA1/2 mutation carriers.
Methods: 68 healthy and cancer-diseased BRCA1/2 germline mutation
carriers were recruited for the LIBRE-1 trial from university hospitals
(Cologne, Kiel and Munich) in Germany. At study entry they were exam-
ined using cardiopulmonary exercise testing, accelerometer assessments
and a questionnaire survey about their physical activity levels during ad-
olescence (age 10 - 19 years) and the socioeconomic status. Additionally,
they received a psychological questionnaire according to the theory of
planned behavior asking about their attitude, intention, normative and
behavior towards physical activity. Multivariate logistic regression models
were used to identify predictors of the womens age-adjusted VO2peak.
Results: Of the 68 participants (median age 42 (IQR: 33 – 50) years),
46 (68%) were cancer survivors. e strongest predictor for a higher age-
related VO2peak in the regression model was a positive attitude towards
physical activity (Odds Ratio (OR) = 3.0; 95% CI = 1.3 – 8.4; p = 0.021).
Neither the cancer-disease status nor the physical activity level during
adolescence had a signicant inuence on the VO2peak of BRCA1/2
mutation carriers in this analysis.
Conclusions: e attitude towards physical activity seems to play a role
in the current VO2peak status in healthy and cancer-diseased BRCA1/2 mu-
tation carriers. Physical activity during adolescence and the health and
socioeconomic status do not inuence VO2peak.
Disclosure Statement: e study was funded by the Deutsche Krebshilfe. ere is
no conict of interest.
994
Impact – Implementing Patients Competence in Oral Breast
Cancer Therapy – A Randomized, Controlled Study of
Standardized Patient Coaching Versus Patient Management
According to Local Practice for Patients with HR Positive HER2
Negative Metastatic Breast Cancer Treated with Abemaciclib
Manfred Welslau1; Naiba Nabieva2,3; Thomas Decker4; Erik Belleville5;
Oliver Knapp5; Lothar Häberle2,3; Peter A. Fasching2,3,6; Hans Tesch7
1Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaenburg,
Aschaenburg, Deutschland
2Department of Gynecology and Obstetrics, University Hospital Erlangen,
Erlangen, Deutschland
3Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen,
Erlangen, Deutschland
4Gemeinschaftspraxis für Hämatologie und Onkologie GbR Ravensburg,
Ravensburg, Deutschland
5ClinSol GmbH & Co. KG, Würzburg, Deutschland
6Institut für Frauengesundheit GmbH (IFG), Erlangen, Deutschland
7Centrum für Hämatologie und Onkologie Bethanien, Frankfurt am Main,
Deutschland
Purpose: Oral agents, like CDK4/6 inhibitors, provide an attractive ap-
proach for the treatment of metastatic breast cancer. However, this type
of therapy requires a high level of self-management competence by the
patient. e non-interventional study (NIS) IMPACT intends to evalu-
ate the eectiveness of a standardized patient education and coaching for
therapy management provided by specially trained oncology nurses re-
garding persistence rate, side eects management and unplanned therapy
interruptions in outpatient oncology care for patients under Abemaciclib
treatment.
Methods: 212 Patients with HR+, HER2- MBC who are treated with Abe-
maciclib according to clinical routine will be enrolled in approx. 30 sites.
Patients will be randomized to standardized patient coaching (based on
MOATT©) or patient management according to local practice, respective-
ly. Follow up is documented for a maximum of 24 weeks.
Results: Data of 212 MBC patients regarding a potential eect of stan-
dardized patient coaching on the persistence rate aer 24 weeks of Abe-
maciclib therapy will be presented. Quality of live data as well as data re-
garding patient reported self-ecacy, side-eects, health related stress and
therapy related knowledge will be presented.
Conclusions: e eectiveness of standardized patient coaching is ob-
served and analyzed in a real-world setting to understand its benets for
MBC patients under Abemaciclib treatment with regard to therapy adher-
ence and patient self-management competence.
Disclosure: Manfred Welslau; Advisory Role: AMGEN, BMS, Celgene, GILEAD,
HEXAL, Janssen, Lilly, medac, NOVARTIS, Roche, SANOFI Expert Testimony:
Ja, BMS; Honorare: AMGEN, astellas, AstraZeneca, Celgene, GILEAD, HEXAL,
Janssen, Lilly, NOVARTIS, Roche, SANOFI;
1007
Prognostic Impact of IGKC in Breast Cancer Patients Treated
with Adjuvant Chemotherapy
Anne-Sophie Heimes; Hannah Krämer; Annette Hasenburg;
Marcus Schmidt
Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und
Fraeungesundheit, Mainz, Deutschland
Background:In previous work we could demonstrate that the presence of
IgKC positive tumor inltrating plasma cells was associated with a better
prognosis in node-negative breast cancer patients who didn’t receive any
adjuvant treatment aer operation and irradiation. In the present study
we evaluated the prognostic signicance of IgKC in breast cancer pa-
tients who were treated with chemotherapy according to the CMF or FEC
scheme in the adjuvant setting.
Methods: IgKC expression was immunohistochemically analyzed in 234
breast cancer patients who received aer operation and irradiation an ad-
juvant chemotherapy according to the CMF or FEC scheme between 1993
and 2001 at the department of gynecology and obstetrics of the university
hospital Mainz with a median follow up of 11 years. From the 234 immu-
nohistochemical stained tumor slides 193 were suitable for evaluation: 78
of the CMF- und 115 of the FEC cohort. e prognostic impact of IgKC
expression was evaluated by Kaplan Meier survival analyses as well as uni
– and multivariate Cox-Regression. Immunohistochemically determined
IgKC expression levels were compared to the corresponding mRNA val-
ues in 65 patients using Spearman correlation.
Results: Kaplan Meier analyses identied IgKC as a prognostic marker in
regard to the MFS: higher IgKC expression was correlated with a better
outcome (p=0.02 Log Rank). Results of univariate Cox Regression con-
rmed the prognostic impact of IgKC expression: patients with a strong
IgKC expression had a longer MFS compared to the patients with a weak
IgKC expression (HR1.931; p=0.025). Multivariate cox regression showed
an independent prognostic signicance of IgKC expression (HR 2.486,
p=0.012). Immunohistochemically determined IgKC correlated signi-
cantly with IgKC mRNA expression (ρ = 0.304; p=0.014).
Conclusion: IgKC expression had independent prognostic impact in the
analyzed cohort of 193 breast cancer patients who received adjuvant che-
motherapy.
1047
A Companion App to Improve Quality of Life and Adherence
to Adjuvant Treatment in Early Breast Cancer Patients
Heike Dr. Jansen1; Kirsten Große Lackmann1; Marko Wilhelm2;
Vera Lorinser3; Alexander Dempf3; Marc Schallehn3; Marion Kiechle1
1Frauenklinik, Technische Universität München, Klinikum rechts der Isar,
München, Deutschland
2Meine Busenfreundin GmbH, München, Deutschland
3Telum GmbH, Business IT Solutions, München, Deutschland
Purpose: Mobile applications (apps) can support cancer patients regard-
ing their needs. e use of apps can reduce symptom burden and increase
adherence for cancer therapy. Non-adherence rates to endocrine therapy
(ET) range from 31% to 73%1. Consequently these patients have a poorer
prognosis due to recurrence, progression and cancer death.
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Methods: In an interdisciplinary approach we developed “Meine Busen-
freundin“ as a companion app. e app provides breast cancer patients
with an instrument to accompany, inform, motivate and support them
from diagnosis up to follow up care. e patient enters some data con-
cerning her disease and person and creates an individual “medical pro-
le”: based on these data she will receive personalized information and
support. By autonomous use she gets a tool for a self-determined contri-
bution to her therapy.
Results: In a pilot study with 30 patients, the app got evaluated and usabil-
ity was veried and conrmed.
Conclusions: is to our knowledge the rst companion app for breast
cancer patients turned out to be acceptable and feasible in a pilot study.
Additionally we set up a protocol for a randomized, prospective, multi-
center clinical trial to search out whether the therapy-conducted loss of
quality of life can be reduced by the use of the app. e burden of the
therapy and its side eects oen result in unauthorized discontinuation
of the therapy by patients. is study shall furthermore nd out, whether
the use of the app can also reduce the discontinuation-rate and therefore
increase adherence to ET and improve outcome.
Reference:
1. Murphy et al, Adherence to adjuvant hormonal therapy among breast cancer
survivors in clinical practice: a systematic review. Breast Cancer Res Treat.
2012 Jul;134(2):459-78.
Disclosure Statement: Government funding for this project is granted by the
Bavarian Ministry of Economic Aairs, Regional Development and Energy. e
funding agency has no role in the design and conduct of the study. Kiechle, M. and
Große Lackmann, K. are equity owners of Meine Busenfreundin GmbH.
Cancer Prevention
Vorträge
899
Risk-Adapted Screening for Prostate Cancer in Young Men –
First Results of the Probase Trial
Peter Albers1,2; Christian Arsov1; Kathleen Herkommer3; Jürgen Gschwend3;
Florian Imkamp4; Markus A. Kuczyk4; Boris Hadaschik5,6;
Glen Kristiansen7; Lars Schimmöller8; Gerald Antoch8; Ernst Rummeny9;
Frank K. Wacker10; Heinz-Peter Schlemmer11; Axel Benner12;
Roswitha Siener13; Rudolf Kaaks14; Nikolaus Becker14
1Department of Urology, Düsseldorf University Hospital, Heinrich-Heine-
University Düsseldorf, Düsseldorf, Deutschland
2Deutsches Krebsforschungszentrum, Cancer Prevention, Heidelberg,
Deutschland
3Technische Universität München, Department of Urology, München,
Deutschland
4Medizinische Hochschule Hannover, Department of Urology, Hannover,
Deutschland
5Universität Heidelberg, Department of Urology, Heidelberg, Deutschland
6Universität Duisburg-Essen, Essen, Deutschland
7UKB Universitätsklinikum Bonn, Institute of Pathology, Bonn, Deutschland
8Universitätsklinikum Düsseldorf, Institute of Diagnostic and Interventional
Radiology, Düsseldorf, Deutschland
9Technische Universität München, Institute of Diagnostic and Interventional
Radiology, München, Deutschland
10Medizinische Hochschule Hannover (MHH), Institute of Diagnostic and
Interventional Radiology, Hannover, Deutschland
11Deutsches Krebsforschungszentrum, Department of Radiology, Heidelberg,
Deutschland
12Deutsches Krebsforschungszentrum, Department of Biostatistics, Heidelberg,
Deutschland
13UKB Universitätsklinikum Bonn, Department of Urology, Bonn, Deutschland
14Deutsches Krebsforschungszentrum, Department of Cancer Epidemiology,
Heidelberg, Deutschland
Background: Prostate cancer (PCa) is the most frequent cancer and sec-
ond leading cause of cancer-related death in men. e German “Prostate
Cancer Early Detection Study Based on a Baseline PSA Value in Young
Men” (PROBASE) aims at improving the specicity of a PSA based
screening while preserving the sensitivity to detect metastatic disease in a
prospective randomized controlled setting.
Methods: Between February 2014 and December 2019, more than 46,500
participants will have been randomized at four study sites in Germany
to an immediate (arm A) and a 5-years deferred (arm B) PSA baseline
measurement at age 45. e combined primary endpoints are the non-in-
feriority of the sensitivity to detect metastasis at age 60 and the superiority
in terms of specicity using a delayed start of screening at age 50.
Results: At the time of last data cut-o, 20,402 (89.16%), 2,141 (9.36%),
and 340 (1.49%) of participants in arm A had initial PSA values of
< 1.5 ng/ml, 1.5-2.99 ng/ml, and >3 ng/ml, respectively. Only 185 were
conrmed with a PSA value > 3ng/ml (0.81% high risk). Mean and medi-
an PSA values in arm A were 0.896 ng/ml and 0.740 ng/ml, respectively.
Participants at high risk had mean and median PSA values of 5.26 ng/ml
and 4.12 ng/ml, respectively. Biopsy was performed in 113 of 185 (61.1%)
men at high risk, 108 (95.6%) of those had a prior mpMRI. us, biopsy
was performed as MRI/ultrasound fusion biopsy with an additional sys-
tematic biopsy (at least 12 cores). All biopsies and PCa were conrmed
by reference pathology. A digito-rectal examination (DRE) as part of the
statutory early detection program in Germany was oered to participants
in arm B and data will be provided from 6.523 participants.
Conclusion: A risk-adapted PSA-based screening strategy at young ages
(45 years) must include a conrmatory PSA value. An updated analysis
of the rst screening round data will be performed aer the end of re-
cruitment with a data-cut o at December 31, 2019. ese results will be
presented.
Funding: Deutsche Krebshilfe, Bonn
Poster
1027
Role of Resident Gynecologists in the Care of Counselees with
Family Cancer Burden - A Needs Analysis
Karen Fechner1; Stephanie Häring2; Friederike Kendel3; Markus Feufel4;
Christine Olbrich1; Dorothee Speiser1
1Klinik für Gynäkologie mit Brustzentrum, Charité – Universitätsmedizin Berlin,
Berlin, Deutschland
2Institut für Geschlechterforschung in der Medizin (GiM), Charité –
Universitätsmedizin Berlin
3Institut für Geschlechterforschung in der Medizin (GiM), Charité –
Universitätsmedizin Berlin, Berlin, Deutschland
4Institut für Psychologie und Arbeitswissenschaft (IPA), Fachbereich
Arbeitswissenschaft, Technische Universität Berlin, Deutschland
Purpose: Investigating the need for and interest in education on genetic
tumor syndromes in gynecology among resident gynecologists.
Methods: An 11-question online survey was conducted from 09-11/2019
and addressed 563 registered gynecologists in Berlin and Brandenburg.
e survey concentrated on the incidence and handling of patients with
family cancer burden in gynecological practices. It focused on the knowl-
edge of resident gynecologists on genetic risk assessment and identi-
cation of patients at risk and their referral to specialized tumor genetic
clinics.
Results: 97 respondents (17,2%) completed the survey. Whereas, 87
gynecologists (89,7%) take family history on a regular basis, only 13
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gynecologists (13,4%) dared to assess the risk of hereditary tumor burden.
Furthermore, knowledge of inclusion criteria for specialized tumor care
consultation was limited among the interviewed gynecologists. erefore,
only 37 gynecologists (38,1%) referred patients to specialized tumor
genetic clinics correctly.
While 59 gynecologists (60,8%) see 1-3 patients per week with gynecolog-
ically relevant cancers in the family, others (37,1%) see 4-5 or more than
5 patients per week.
74 respondents (76,3%) agreed, that comprehensive knowledge about he-
reditary cancer risks could improve the care of their patients.
Finally, 89 gynecologists (91,8%) stated interest in further education on
genetic tumor syndromes in gynecology and 86 gynecologists (88,7%) al-
ready registered for the planned training course.
Conclusions: is survey emphasizes the high relevance of genetic tumor
syndromes in outpatient gynecological care. e self-assessments of gyne-
cologists showed some uncertainties in risk assessment, inclusion criteria
and the referral to specialized centers. In this context, we develop a train-
ing course based on blended learning that is tailored to the special needs
of gynecologists in outpatient practices.
Central Nervous System Tumors
Poster
903
Impact on Long-Term Survival of Pre-OP Frailty of Patients
with Limited Brain Metastases
Micha Peeck1; Tobias Pukrop2; Veit Rohde3; Tim Beißbarth4;
Manuel Nietert4; Benjamin Kirchner5; Annalen Bleckmann1
1Medizinische Klink A, Universitätsklinikum Münster, Münster, Deutschland
2Klinik und Poliklinik für Innere Medizin III, Universitätsklinikum Regensburg
Regensburg, Deutschland
3Neurochirurgische Klinik, Universiätsmedizin Göttingen, Göttingen,
Deutschland
4Instituts für Medizinische Bioinformatik, Universitätsmedizin Göttingen,
Göttingen, Deutschland
5Klinik für Hämatologie und internistische Onkologie, Universitätsmedizin
Göttingen, Göttingen,
Introduction: Brain metastasis represents a major complication of many
oncological diseases with a signicantly shorter overall survival. In view
of the generally poor prognosis, clinical decision making between not
harming the patient and potentially withholding a therapeutic option can
sometimes be very challenging. us the aim of this study was to identify
whether easily leviable scores may be potentially useful to predict survival
in this setting.
Methods: Patients within our retrospective cohort (n=100, median age
63.6 years) had undergone brain surgery because of one or more brain
metastases in our institution. is cohort includes 52 patients with NS-
CLC, 27 patients with breast cancer, 8 patients with colorectal carcinoma
and 13 patients with kidney cancer. To categorize these, we used dierent
score systems which were capable to evaluate the patient in relation to
self-suciency, activity and self-determination as part of activities of dai-
ly living. e used scores were: ECOG-Status, Karnofsky-Index, Barthel-
Index, ASA-Classication, Katz-Index. Pre-processing and analysis of the
data was implemented using KNIME, while we used the R-plugin nodes
to perform the nal statistical tests with R.
Results: Our analysis reveals that most of the frailty scores we tested on
our patient population are able to give a reliable prediction on the overall
survival aer brain metastasis surgery. e survival rates decrease signi-
cantly with a lower score in all tested score systems, except the ASA-Risk
score. In particular, a Katz Index <6 was identied to have a signicant
correlation with a lower cause specic survival (CSS) (HR 3.33, 95%-CI
[2.17-5.00]; p-Value = 9.6*10-9).
Conclusion: Pre-operative frailty status measurements by indices of daily
living represent a powerful predictor for overall survival aer resection
of brain metastases. Especially the easy and fast applicable Katz-Score
is a very helpful pre-operative tool to assess the pre-operative status,
which could be additionally included in clinical decision making in daily
practice.
965
The Prognostic Role of H3K27 Trimethylation in Meningioma
Felix Behling1,2,3; Christina-Katharina Fodi1,2,3; Irina Gepfner-Tuma4;
Kathrin Machetanz1,2,3; Kristina Kaltenbach2,3,5; Mirjam Renovanz1,2,3;
Marco Skardelly1,2,3; Farshad Nassiri6; Gelareh Zadeh6; Marcos Tatagiba1,2,3;
Ghazaleh Tabatabai1,2,3,5; Jens Schittenhelm2,3,7
1Klinik für Neurochirurgie, Universitätsklinik Tübingen, Tübingen, Deutschland
2Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart,
Tübingen, Deutschland
3German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen,
Deutschland
4Klinik für Neurologie, Universitätsklinikum Jena, Jena, Deutschland
5Abeiltung für Neurology und interdisziplinäre Neuro-Onkologie,
Universitätsklinik Tübingen, Tübingen, Deutschland
6Department of Surgery, Division of Neurosurgery, University of Toronto,
Toronto, Kanada
7Institut für Neuropathologie, Universitätsklinik Tübingen, Tübingen,
Deutschland
Purpose: e prognostic role of the histone methylation H3K27 in me-
ningioma has been described recently. e H3K27 trimethylation status
can be detected immunohistochemically and could therefore be integrat-
ed into the routine diagnostic workow to provide prognostic informa-
tion for the clinical management of meningioma patients. e aim of this
study was to assess the prognostic value of H3K27 histone trimethylation
in a large single center cohort of meningiomas with dened clinical sub-
groups.
Methods: We included 429 patients with complete clinical data and avail-
able tissue who underwent meningioma resection between April 2011
and December 2015 at the University Hospital Tübingen. We performed
H3K27me3 immunohistochemical staining, which was evaluated by two
independent investigators. Correlation with clinical parameters (WHO
grade, brain invasion, Simpson grade, age, gender, progression free sur-
vival) was performed using univariate and multivariate cox regressions as
well as Fishers exact and Log-Rank test.
Results: At the time of abstract submission, a total of 429 meningiomas
were analyzed with a female to male ratio of 3.2, mean age of 59 years
(range 15.84 – 89.95) and mean follow-up at 31 months (range 1.76 –
95.72). Univariate analysis showed a signicant negative prognostic im-
pact of male gender (p=0.0236), WHO grade II/III (p=0.0057), Simpson
grade >2 (p<.0001) and H3K27me3 loss (p=0.0007). In the multivariate
analysis Simpson grade and H3K27me3 status remained independent
prognostic factors for meningioma recurrence (p = 0.0001 and 0.0084,
respectively). H3K27 trimethylation loss was more common in male pa-
tients explaining the loss of prognostic impact of gender aer inclusion of
the histone methylation status in the multivariate analysis.
Conclusions: Loss of the trimethylation of H3K27 is an independent
prognostic factor and in line with prior studies. Further correlations with
clinical subgroups will be presented. Our data could help to continue the
discussions on the clinical utility of H3K27me3 staining in meningioma.
Conict of interest: None.
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Developmental Therapeutics: Cytotoxic Chemotherapy
Poster
914
Anti-Tumor Activity of CT913 In Vitro and In Vivo
Ralf Axel Hilger1; Nina Clasen1; Sebastian Hoenes1; Hans-Joachim Zeiler2
1Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Westdeutsches
Tumorzentrum, Essen, Deutschland
2Creative Therapeutics GmbH, Wuppertal, Deutschland
Purpose: CT913 is an anti-tumoral compound with a novel chemical
structure. CT913 was designed not only to be an eective compound
against cancer but also to be well tolerated in humans.
Methods: Dierent human tumor cell lines were maintained in specic
culture medium. e cells were incubated with CT913 in a time depen-
dent manner. Cell cycle analysis and apoptosis were accessed by ow cy-
tometry using propidium iodide (PI) and Annexin-V/PI. Proteins, such
as p21, p53, phospho-p38 and phospho-Erk1/2, were detected by west-
ern blotting. Expression of phospho-Erk1/2 in the cells was conrmed by
ow cytometry aer PMA stimulation. For metabolism studies, RP-HPLC
methods combining UV- and MS-spectroscopy were used. A benzidine
induced breast cancer and a human melanoma xenogra mouse model
were used for animal studies.
Results: CT913 is a novel broad-spectrum antitumor agent inducing
apoptosis in dierent human tumor cells. In addition, one metabolite
(M1) of CT913 was investigated. CT913 and M1 both induced apoptosis
via cell cycle arrest in G1/S aer up-regulation of p21 and p53 and in-
creased DNA-Damage-Response (DDR) over a longer time period result-
ing in metabolic and genomic instability. CT913 was designed according
to Reverse-Metabolic-Drug-Design (RMDD) rules to deliver a well-toler-
ated anticancer drug. CT913 demonstrated antitumor activity in human
breast cancer and malignant melanoma animal models.
Conclusions: CT913 shows an unique ecacy prole, triggering a del-
eterious metabolic cascade by addressing dierent decisive targets, such
as damaging tumor metabolism on DNA-level, simultaneously blocking a
specic repair system, triggering genomic and metabolic instability, and
production of aberrant proteins possibly appearing on the surface of tu-
mor cells (epigenetic changes) allowing the natural host defense system to
recognize and attack these transformed cells.
Disclosure Statement: Nothing to declare
Developmental Therapeutics: Immunotherapy/Cellular Therapy
Vorträge
956
The B Cell Maturation Antigen (BCMA) Chimeric Antigen
Receptor (CAR) T Cell Therapy Idecabtagene Vicleucel (Ide-
Cel; Bb2121) in Relapsed and Refractory Multiple Myeloma
(Rrmm): Outcomes from a Phase 1 Study Support the Phase 3
Karmma-3 Study Design to Compare IDE-Cel Versus Standard
Triplet Regimens
Hermann Einsele1; Marc Raab2; Nicolaus Kroeger3; Roland Fenk4;
Christoph Scheid5; Nikhil Munshi6; Fabio Petrocca7; Kristen Hege8;
Steven Novick8; Noopur Raje9; James Kochenderfer10
1Julius-Maximilians-Universität Würzburg, Würzburg, Deutschland
2Universitätsklinikum Heidelberg, Heidelberg, Deutschland
3Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
4Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland
5Klinikum der Universität Köln, Köln, Deutschland
6Dana-Farber Cancer Institute, Boston, United States
7Blue Bird Bio, Cambridge, United States
8Bristol-Myers Squibb, Summit, United States
9Massachusetts General Hospital Cancer Center, Boston, United States,
10National Cancer Institute, NIH, Bethesda, United States
Purpose: Despite new treatment options for myeloma, poor overall sur-
vival has been reported in patients with RRMM aer >3 prior therapies.
e CRB-401 phase 1 study (NCT02658929) evaluated ide-cel, a BCMA
CAR T-cell therapy, in RRMM patients who received ≥3 prior lines of
therapy, including a proteasome inhibitor and an immunomodulatory
agent, or were refractory to both drug classes. e objective response
rate was 85% (45% complete response rate) and median progression-free
survival (PFS) was 11.8 months (95% CI, 6.2−17.8.1 All 16 evaluable re-
sponding patients were minimal residual disease (MRD)-negative (≤10-4
nucleated cells).1 Ide-cel has been granted PRIME eligibility in RRMM
by the European Medicines Agency. KarMMa, the phase 2 pivotal study
(NCT03361748), has completed accrual (140 patients as of November
2018). Informed by these studies, KarMMa-3 (NCT03651128), a phase
3 multicenter randomized trial, is designed to conrm the ecacy and
safety of ide-cel in earlier treatment lines.
Methods: KarMMa-3 compares the ecacy and safety of ide-cel to those
of standard triplet regimens in RRMM. Eligible patients have received 2–4
prior regimens, including an immunomodulatory drug, proteasome in-
hibitor, or daratumumab, and are refractory to their last therapy. Patients
will be randomized 2:1 to receive either ide-cel treatment (150–450 × 106
CAR+ T cells) or a standard triplet regimen such as daratumumab, po-
malidomide, and dexamethasone (DPd); daratumumab, bortezomib, and
dexamethasone (DVd); or ixazomib, lenalidomide, and dexamethasone
(IRd); at the investigators discretion. e primary endpoint is PFS. Sec-
ondary endpoints include overall survival, safety, MRD-negative status,
and health-related quality of life. Patient accrual is ongoing.
Conclusions: Data from CRB-401 in patients with RRMM who received
≥3 prior therapies support investigating ide-cel in earlier treatment lines,
as planned in KarMMa-3.
Reference:
1. Raje N, et al. Anti-BCMA CAR T-Cell erapy bb2121 in Relapsed or Refrac-
tory Multiple Myeloma. N Engl J Med. 2019;380(18):1726-1737.
997
Initial Results from a Phase II Study (TACTI-002) in Metastatic
Non-Small Cell Lung or Head and Neck Carcinoma Patients
Receiving Eftilagimod Alpha (Soluble Lag-3 Protein) and
Pembrolizumab
Berhard Doger1; Margarita Majem2; Eriqueta Felip3; Enric Carcereney4;
Tim Clay5; Frederic Triebel6
1Fundación Jiménez Diaz, Madrid, Spanien
2Hospital de la Santa Creu i Sant Pau, Barcelona, Spanien
3Vall d’Hebron University Hospital, Barcelona, Spanien
4Hospital Germans Trias i Pujol, Badalona, Spanien
5St John of God Subiaco Hospital, Subiaco, Australien
6Immutep S.A.S., Paris, Frankreich
Purpose: Eilagimod alpha (ei) is a soluble LAG-3 protein that binds
to a subset of MHC class II molecules to mediate antigen presenting cell
(APC) activation and then CD8 T-cell activation. e stimulation of the
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dendritic cell network and subsequent T cell recruitment with ei may
lead to stronger anti-tumor responses than observed with pembrolizumab
alone. Combining an APC activator with an immune checkpoint inhibitor
aims to increase ecacy without additional toxicity. We hereby report ini-
tial results of a phase II trial (NCT03625323).
Methods: e study is based on a Simons 2-stage design, with objec-
tive response rate (ORR) as primary endpoint. Secondary endpoints in-
clude progression free and overall survival, PK, PD and immunogenicity.
During the 1st stage of the study, patients (pts) regardless of PD-L1 expres-
sion are recruited into: A: 1st line, PD-X naïve NSCLC; B: 2nd line, PD-X
refractory NSCLC; C: 2nd line PD-X naive HNSCC. Additional pts (N2)
will be recruited for each part if the pre-specied threshold for ORR is
met. Up to 109 pts will be enrolled. Ei is administered as 30 mg subcu-
taneous injection every 2 weeks for 8 cycles and then every 3 weeks for 9
cycles. Pembrolizumab is administered at a standard dose (200 mg intra-
venous infusion every 3 weeks for up to 2 years). e study was approved
by ethics committees and institutional review boards.
Results: Between Mar and Dec 2019, 42 pts were enrolled. e mean age
was 66 years (range 48-84) and 74 % were male. e ECOG was 0 in 57 %
and 1 in 43 % of the pts, respectively. e most common (≥ 10%) adverse
events being cough (26%), asthenia (21 %), decreased appetite (17 %), fa-
tigue (17 %), diarrhea (14 %) and dyspnea (14 %). All pts of part A (n=17)
are evaluable for ecacy. Seven pts (42 %) had a partial response and six
(35 %) pts had stable disease according to iRECIST leading to an ORR of
42 %. 11 (65 %) pts are still under therapy and 10 (59 %) have reached the
6 months landmark.
Conclusions: irty (30) mg ei s.c. every 2 weeks in combination with
pembrolizumab is safe and shows encouraging antitumor activity in all
comer PD-L1 1st line NSCLC.
1040
Enhanced Recruitment and Immunosuppression-Shielding
Enables T Cell Therapy in Solid Tumors
Bruno Loureiro Cadilha1; Klara Dorman1; Duc Huynh1; Theo Lorenzini1;
Mira Vänttinen1; Mohamed-Reda Benmebarek1; Stefan Stoiber1;
Javier Suarez-Gosalvez1; Stefan Endres1; Sebastian Kobold1,2
1Center of Integrated Protein Science Munich and Division of Clinical
Pharmacology, Department of Medicine IV, Klinikum der Universität München,
Munich, Germany, Member of the German Center for Lung Research
2German Center for Translational Cancer Research (DKTK), partner site Munich,
Germany
Purpose: CART cell therapy is remarkably successful in patients with
hematological malignancies, in some cases inducing durable remissions.
However, it remains ineective in solid tumors, due to limited access to
the cancer site and the subsequent immunosuppression. Overcoming
these limitations is critical to enable CAR T cell therapy translation into
solid tumors. We propose that engineering CAR T cells with the C-C
chemokine receptor 8 (CCR8) can improve migration towards solid
tumor tissues. Further, simultaneous engineering with a dominant-
negative TGF-β-receptor 2 (DNR) allows T cell proliferation despite
TGF-β, a well-studied cytokine that suppresses T cell cytotoxic potential
and proliferative capacity, that can be found in high amounts in certain
solid tumors, such as pancreatic adenocarcinoma.
Methods: We used 6- to 10-week-old female mice from C57Bl/6 or NSG
strains and experiments were performed in a blinded and randomized
manner. e tumor cell lines used for this study were either Panc02,
Panc02-CCL1, Panc02-OVA-EpCAM, or SUIT-2-MSLN-CCL1. Eects
have been assessed through ow cytometry, multi-photon intra-vital mi-
croscopy and tumor size measurements.
Results: We observed improved functionality of our CCR8-DNR CAR
T cells compared to the control conditions. In vivo we demonstrated
the enhanced inltration capacity conferred by CCR8 through intra-vi-
tal multi-photon microscopy. Pancreatic tumor challenge experiments
showed, both for murine syngeneic and human xenogra models, sig-
nicant reduction of tumor burden with improved survival rates. Lastly,
analysis of a large sample of patients led to identication of genetic hall-
marks that sustain the employment of this rationale not only to pancreatic
tumors but also breast, colon and skin tumors.
Conclusion: Our results show that CCR8 and DNR can eectively be em-
ployed to render CAR T cell therapy eective in solid tumors.
Poster
880
Medical Gas Plasma Technology – An Emerging
Immunostimulatory Anticancer Agent
Sander Bekeschus1; Eric Freund2; Steen Emmert3
1Leibniz Institute for Plasma Science and Technology, ZIK plasmatis, Greifswald,
Deutschland
2Greifswald University Medical Center, Department of General Surgery,
Greifswald, Deutschland
3Rostock University Medical Center, Clinic and Policlinic for Dermatology and
Venereology, Rostock, Deutschland
Purpose: erapy of skin cancer including malignant melanoma has
made signicant progress in the past years. However, a fraction of patients
still does not benet from therapy or acquires drug resistant cancers, mo-
tivating the need of new therapeutic avenues. Medical gas plasma technol-
ogy is an emerging tool to reduce tumor growth in vitro and in vivo that
mainly acts via local release of a plethora of reactive oxygen and nitrogen
species.
Methods: Human and murine melanoma cells were treated in vitro with
plasma technology. Cellular function and viability as well as immuno-
genic properties were characterized. In a syngeneic B16F10 melanoma
model, tumors were exposed to either gas plasma or positive control
imiquimod. e intratumoral immune inltrate and splenic leukocytes
were characterized by multicolor ow cytometry. Moreover, mice were
vaccinated with plasma-treated melanoma cells and later re-challenged
with viable melanoma cells to investigate the extent of immunoprotection
via ROS-induced tumor cell death.
Results: Gas plasma induced cell death was observed in a pro-immuno-
genic fashion in vitro and in vivo. In mice, plasma-treated tumors as well
as positive controls showed elevated levels of inltrated leukocytes. Splen-
ic immune cells re-stimulated with melanoma cells in vitro showed an
enhanced activation. Moreover, 50% of animals were protected from mel-
anoma growth in mice vaccinated with plasma-treated melanoma cells.
Conclusions: Medical gas plasma technology may serve as novel tool to
target skin cancer in an immunogenic fashion.
Disclosure Statement: Nothing to disclose.
933
RNA Editing as a tool to Improve Sensitivity to
Immunotherapy
Riccardo Pecori1; Beatrice Casati1; Annette Arnold1; Nina F. Papavasiliou1
1German Cancer Research Centre (DKFZ), Division of Immune Diversity,
Heidelberg, Deutschland
Purpose: Immunotherapy had drastically improved success in treatment
of cancers. But despite this remarkable clinical success many patients do
not respond to immunotherapy, or develop therapeutic resistance. For
this reason, the need for development of novel strategies that sensitize tu-
mours to immunotherapy currently in use, is urgent.
Methods: Mutations within a tumour lead to a higher sensitivity to im-
munotherapy1. It is assumed that increased mutation correlates with an
increase in neoepitope/antigen formation, and therefore increased sen-
sitivity to T cell attack. erefore, a method leading to increase neoepi-
tope formation specically in cancer cells would be optimal solution to
sensitize tumours to immunotherapy. e RNA editing enzyme ADAR1
is highly expressed in many human tumours and can be re-targeted to
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2018
coding regions in a sequence-specic manner. e main goal here is to
test whether ADAR1 re-targeting to coding regions will increase the level
of tumour “neoantigenicity” and thus render the tumour sensitive to im-
mune checkpoint blockade.
Results: All the available systems to induce RNA editing were evaluated
in their eciency to re-code, exogenously and endogenously expressed,
transcripts. Dierently from Cas13b based system2, lambda-N-ADAR and
SNAP-ADAR technologies3,4 were able to induce editing in both contexts.
Conclusions: Our data show that RNA editing can be retargeted to re-
code specic transcripts. ese results disclose the possibility to use RNA
editing to create “neo-epitopes” within cancer cells, sensitizing them to
recognition and subsequent killing/clearance by T cells.
References:
1. Samstein, R. M. et al. Nature Genetics (2019)
2. Cox, D. B. T. et al. Science (80-. ). 358, 1019–1027 (2017)
3. F, Montiel-Gonzalez, M. et al. Proc. Natl. Acad. Sci. U.S.A. 110, 18285–18290
(2013)
4. Vogel, P. et al. Nat. Methods 15, 535–538 (2018)
Disclosure Statement: Re-targeted RNA editing can be used to generate “neo-epi-
topes” within cancer cells.
972
Innovative Antibody Fragment-Based Targeted Constructs
as Bispecic Treatment Option for Medulloblastoma
Judith Niesen1; Christina Krüger2; Ulrich Schüller3
1Hamburg, Department of Pediatric Hematology and Oncology, University
Medical Center Hamburg-Eppendorf & Research Institute Childrens Cancer
Center, Hamburg, Deutschland
2Hamburg, Department of Pediatric Hematology and Oncology, University
Medical Center Hamburg-Eppendorf & Research Institute Childrens Cancer
Center, , Hamburg, Deutschland
3Department of Pediatric Hematology and Oncology, University Medical Center
Hamburg-Eppendorf & Research Institute Children’s Cancer Center, Institute of
Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg,
Deutschland
Purpose: Medulloblastoma (MB), the most frequent malignant brain
tumor in children shows overexpression of the EGF-receptor. Radio-and
chemotherapy oen results in severe long-term side eects in children.
erefore, targeted treatment options are urgently needed. Our innovative
approach is to evaluate bispecic T-cell engagers (BiTEs) with already
established EGFR-specic scFvs as targeted therapy for MB. e structure
and specicity allows a BiTE to link a T cell to a tumour cell, stimulating
T cell activation, tumour killing and cytokine production. Using BiTEs
in MB, they must cross the Blood-Brain-Barrier (BBB). To evaluate the
diusion kinetics of BiTEs, we want to test them in a novel in vitro-BBB-
model.
Methods: EGFR-overexpression in MB-cell lines, human and mouse
MB-biopsies was tested in ow cytometry, immunohistochemistry or
western blot. To obtain BiTEs the EGFR-specic scFvs were fused to a
CD3-specic scFv joined by a exible linker. e BiTEs were expressed in
HEK-293T cells and puried using the His-Tag. Eector- and target-cell
specicity was demonstrated via ow cytometry. To test the cytotoxicity
apoptosis and ow cytometry based assays were used.
Results: Surface EGFR-overexpression was proven in mouse and human
SHH-MB. BITEs show specic binding to eector and to EGFR-expressing
MB-cells. Human PBMCs were incubated with various concentrations of
BiTES and activation was conrmed using anti-CD69 staining. e BiTEs
demonstrate specic apoptotic eects in a 5:1 eector to target cell ratio.
Conclusions: EGFR-specic BiTEs show rst promising results in
MB and will be tested in a BBB-model. e latter will be composed of
human inducible pluripotent stem cells and MB cells in the basolateral
compartment. Having a functional cloning/expression system available,
the target-scFv can be exchange by novel antigens to obtain new
immunotherapeutic options.
Disclosure Statement: e authors disclose no conict of interest.
976
Safety and Ecacy Results From Transcend NHL 001, a
Multicenter Phase 1 Study of Lisocabtagene Maraleucel
(Liso-Cel) In Relapsed/Refractory (R/R) Large B-Cell
Lymphoma (LBCL)
Jeremy Abramson1; M. Lia Palomba2; Leo Gordon3; Matthew Lunning4;
Michael Wang5; Jon Arnason6; Amitkumar Mehta7; Enkhtsetseg Purev8;
David Maloney9; Charalambos Andreadis10; Alison Sehgal11;
Scott Solomon12; Nilanjan Ghosh13; Tina Albertson14; Jacob Garcia14;
Ana Kostic14; Daniel LI14; Yeonhee Kim14; Tanya Siddiqi15
1Massachusetts General Hospital Cancer Center, Boston, United States,
2Memorial Sloan Kettering Cancer Center, New York, United States,
3Northwestern University, Feinberg School of Medicine, Robert H. Lurie
Comprehensive Cancer Center, Chicago, United States
4University of Nebraska Medical Center, Omaha, United States
5University of Texas MD Anderson Cancer Center, Houston, United States
6Beth Israel Deaconess Medical Center, Boston, United States
7University of Alabama at Birmingham, Birmingham, United States
8University of Colorado School of Medicine, Aurora, United States
9Fred Hutchinson Cancer Research Center, Seattle, United States
10University of California, San Francisco, United States
11University of Pittsburgh Medical Center, Pittsburgh, United States
12Immunotherapy Program, Northside Hospital Cancer Institute, Atlanta, United
States
13Levine Cancer Institute, Atrium Health, Charlotte, United States
14Juno Therapeutics, a Bristol-Myers Squibb Company, Seattle, United States
15City of Hope National Medical Center, Duarte, United States
Purpose: To evaluate the safety, antitumor activity, and PK of liso-cel in
R/R LBCL (NCT02631044).
Methods: Patients (pts) aged ≥18 y had R/R DLBCL not otherwise speci-
ed, HGBCL with MYC and BCL2 and/or BCL6 rearrangements, PMBCL,
or FL grade 3B aer ≥2 lines of therapy, and ECOG PS of 0‒2. Pts with
mild/moderate organ dysfunction and secondary CNS lymphoma were
eligible. Bridging therapy was allowed. Liso-cel was given at 50 × 106 (dose
level [DL]1), 100 × 106 (DL2), or 150 × 106 (DL3) viable CAR+ T cells.
Primary end points were treatment-emergent adverse events (TEAEs) and
ORR. Secondary end points were CR rate, duration of response (DOR),
progression-free survival (PFS), and overall survival (OS).
Results: Of 344 pts leukapheresed, 269 received liso-cel (DL1, n = 51; DL2,
n = 177; DL3, n = 41). Median age was 63 y (range, 18‒86 y; ≥65 y, 42%;
≥75 y, 10%). 26% of pts had ≥4 lines of prior therapy (median, 3; range,
1‒8), 67% were chemorefractory, 44% had never achieved CR, and 59%
had bridging therapy. 25 pts received liso-cel as outpatients. Outcomes
were similar across DLs, so data were pooled. 79% of pts had grade ≥3 TE-
AEs, mostly cytopenias. 47% of pts had CRS and/or NEs, with late onset
(median, 5 and 9 days, respectively). Grade ≥3 CRS (2%) and NE (10%)
incidence was low. Four grade 5 liso-cel–related TEAEs occurred. Safety
was similar among pt subgroups. All primary and secondary ecacy end
points were met. Of 256 ecacy-evaluable pts, ORR was 73% (95% CI,
67‒78); CR rate was 53% (95% CI, 47‒59). Responses were similar across
pt subgroups. Median DOR was not reached (NR; 95% CI, 8.6‒NR) with
12.0 mo of median follow-up; median DOR for pts in CR was NR (95%
CI, NR‒NR). Median PFS was 6.8 mo (95% CI, 3.3‒14.1). Median OS was
21.1 mo (95% CI, 13.3‒NR).
Conclusions: Liso-cel showed durable clinical activity with a favorable
safety prole across R/R LBCL histologic subgroups and in pts with poor
prognosis, including chemotherapy refractory, older age, comorbidities,
and high tumor burden. Incidence of severe CRS and NEs was low, with
late onset, allowing for outpatient administration.
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Developmental Therapeutics: Molecular Therapeutics
Poster
931
Eciency and Toxicity of Lenvatinib in Advanced HCC in Later
Treatment Lines
André Jefremow1; Marco Wiesmüller2; Rachel Amanda Rouse1;
Peter Dietrich1; Andreas Emanuel Kremer1; Maximilian Josef Waldner1;
Markus Friedrich Neurath1; Jürgen Siebler1
1Universitätsklinikum Erlangen, Medizinische Klinik 1, Erlangen, Deutschland
2Universitätsklinikum Erlangen, Radiologisches Institut, Erlangen, Deutschland
Purpose: Until 2018 sorafenib was the only rst-line systemictreatment
option for advancedhepatocellular carcinoma (HCC). Ten years later a
new agent, called lenvatinib, showed equal eciency in comparison to
sorafenib. Currently sorafenib and lenvatinib are options for rst line
treatment with regorafenib, cabozantinib and ramucirumab (if alpha fe-
toprotein > 400 ng / ml) as second-line treatment choices. Yet, it has so
not demonstrated, if lenvatinib is an option for a treatment line beyond
the second.
Methods: In this study, we selected 5 patients with advanced HCC from
our hospital, who had been treated with local ablative procedures as well
as at least three dierent systemic therapies before receiving lenvatinib.
Retrospective analysis was performed to investigate clinical and radiolic
response rates as well as side eects.
Results: 3/5 patients achieved regression in third and fourth treatment
lines. One patient showed stable disease, and only one of these ve pa-
tients showed a mixed response. e toxicity prole was heterogeneous.
One patient developed a mild hand-foot syndrome. Another one evolved
hypertension. One patient developed proteinuria leading to stop treat-
ment. Developing psychiatric disorder, which ws possibly associated with
lenvatinib could be seen in one patient. Response was independent of the
underlying cause of HCC.
Conclusions: Lenvatinib is a promising agent for treating advanced HCC
in later treatment lines and revealed a tolerable toxicity prole.
References:
1. Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, u.a. Lenvatinib
versus sorafenib in rst-line treatment of patients with unresectable hepa-
tocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet.
2018;391(10126):1163–73.
2. Personeni N, Pressiani T, Rimassa L. Lenvatinib for the treatment of unre-
sectable hepatocellular carcinoma: evidence to date. J Hepatocell carcinoma.
2019;6:31–9.
Disclosure Statement: AEK: Speaker fee from Eisai
950
The Eect of the Triazene Compound CT913 on Ovarian
Cancer Cells in Vitro and its Interaction with PARP-Inhibitors
Catharina Wichmann1; Jan Dominik Kuhlmann1; Daniel Martin Klotz1;
Hans-Joachim Zeiler2; Ralf Axel Hilger3; Pauline Wimberger1
1TU Dresden, Department of Gynecology and Obstetrics
2Creative Therapeutics GmbH, Wuppertal
3University Hospital of Essen, Department of Medical Oncology, West German
Cancer Center
Purpose: e identication of innovative therapeutic strategies for
ovarian cancer, extending the therapeutic spectrum of PARP-inhibition
(PARPi) beyond HR-deciency, is of high clinical interest. In this regard,
the combination of PARPi with either biological anti-cancer agents
or chemotherapy is a promising strategy for dening new therapeutic
standards. Here, we analysed the therapeutic eect of novel triazene
derivatives, including the drug CT913 and its metabolite CT913-M1 on
ovarian cancer cells and describe their interaction with PARPi.
Methods: In vitro assays for drug characterization were applied in a panel
of six ovarian cancer cell lines.
Results: CT913 treatment conferred a dose-dependent reduction of cell
viability in a set of platinum-sensitive and platinum-resistant ovarian can-
cer cell lines with an IC50 in the micro- to almost millimolar range (107-
940µM), whereas its metabolite CT913-M1 was about 10-fold more po-
tent with an IC50 of 17-93µM. Platinum-resistant Res2-Igrov-1 cells were
more sensitive so CT913-M1 treatment than parental platinum-sensitive
Igrov-1 cells. However, in a combined treatment with cisplatin (CP), nei-
ther CT913 nor CT913-M1 increased the cytotoxic eect of CP. CT913
and CT913-M1 alone were more eective in BRCA1-decient compared
to isogenic BRCA1-procient ovarian cancer cells, indicating that homo-
logues recombination repair may contribute to its mechanism of action.
As our key nding, we showed that CT913 sensitized for Olaparib treat-
ment, independently of BRCA-1 status.
Conclusion: is is the rst study, suggesting the triazene drug class
CT913 as potential combination candidate for extending the therapeutic
spectrum and window of PARPi.
Disclosure Statement: e authors declare that no conict of interest exists.
991
Updated Ecacy and Safety of Entrectinib in Patients (PTS)
with NTRK Fusion-Positive (NTRK+) Tumors: Integrated
Analysis of STARTRK-2, STARTRK-1, and ALKA-372-001
Gunnar Folprecht1; Christian Rolfo2; Rafal Dziadziuszko3; Robert Doebele4;
George Demetri5; Brian Simmons6; Xinhui Huang6; Bethany Pitcher7;
Luis Paz-Ares8
1University Hospital Carl Gustav Carus, University Cancer Center UCC/NCT,
Medical Dept I, Dresden, Deutschland
2Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of
Maryland, Baltimore, MD, United States
3Department of Oncology and Radiotherapy, Medical University of Gdansk,
Gdansk, Poland
4Division of Medical Oncology, University of Colorado Cancer Center, Aurora,
CA, United States
5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston,
United States
6Genentech, Inc., South San Francisco, CA, United States
7F.Homann La-Roche, Basel, Schweiz
8Department of Medical Oncology, Hospital Universitario 12 de Octubre,
Madrid, Spanien
Purpose: Entrectinib is a systemic and CNS-active, potent inhibitor of
TRKA/B/C and ROS1. Primary data from integrated ecacy and safety
analyses (6 mo follow-up) from clinical trials have shown that entrectinib
is a promising option for pts with NTRK+ solid tumors; blinded inde-
pendent central review (BICR) objective response rate (ORR) was 57.4%
(95% CI 43.2–70.8). We show longer follow-up data from this integrated
analysis.
Methods: Pts with locally advanced/metastatic NTRK+ solid tumors con-
rmed by nucleic acid-based methods and enrolled in global (>150 sites,
15 countries) Phase 1/2 entrectinib trials (ALKA [EudraCT 2012-000148-
88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) were
included. Tumors were assessed aer 4 wks (Cycle 1) then every 8 wks.
Scans underwent BICR using RECIST v1.1. Primary endpoints were ORR
and duration of response (DOR) by BICR. Secondary endpoints included
overall survival (OS); ORR and DOR in pts with and without baseline
CNS disease; intracranial (IC) ORR and DOR in pts with baseline CNS
disease; safety.
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Results: ere were 54 adults in the ecacy-evaluable population with
advanced/metastatic NTRK+ solid tumors, including pts with baseline
CNS metastases. As of Oct 30, 2018 (additional 5 mo follow-up), BICR
ORR was 59.3% (95% CI 45.0–72.4); complete responses n=4 (7.4%). Me-
dian BICR DOR was 12.9 mo (95% CI 7.9–NE) and median OS was 23.9
mo (95% CI 16.8–NE). Per baseline CNS status, BICR ORR was 58.3%
(95% CI 27.7–84.8) and 59.5% (95% CI 43.3–74.4) and median DOR was
NE (95% CI 4.2–NE) and 12.9 mo (95% CI 7.9–NE) for pts with (n=12)
and without (n=42) CNS disease, respectively. IC ORR was 54.5% (95% CI
23.4–83.3) and median IC DOR by BICR was NE (95% CI 6.7–NE). En-
trectinib was well tolerated with a safety prole consistent with previously
reports; there were no new or unexpected safety ndings.
Conclusions: In line with the primary data, these results at an additional
5 mo of follow-up show that entrectinib induced clinically meaningful,
durable systemic and intracranial responses in pts with NTRK+ solid tu-
mors.
995
Genomic Landscape of Entrectinib Resistance from Circulating
Tumor DNA (CTDNA) Analysis in STARTRK-2
Robert C. Doebele1; Rafal Dziadziuszko2; Alexander Drilon3; Alice T. Shaw4;
Jürgen Wolf5; Anna F. Farago4; Lucas Dennis6; Todd Riehl7;
Brian Simmons7; Charlie Wu7; Ching-Wei Chang7; Voleak Choeurng7;
Timothy R. Wilson7
1Division of Medical Oncology , University of Colorado, Aurora, CO, United
States
2Department of Oncology and Radiotherapy, Medical University of Gdansk,
Gdansk, Poland
3Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of
Medicine , Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical
College, New York, NY, United States
4Center for Thoracic Cancers, Massachusetts General Hospital, Boston, MA,
United States
5Center for Integrated Oncology, University Hospital of Cologne, Cologne,
Deutschland,
6Foundation Medicine, Cambridge, MA, United States
7Genentech, Inc., South San Francisco, CA, United States
Purpose: Entrectinib is a small molecule inhibitor of ROS1 and TRKA/
B/C with deep and durable responses in ROS1 fusion-positive NSCLC
(ROS1+) and NTRK1,2,3 fusion-positive solid tumors (NTRK+). Despite
clinically meaningful activity, progression on entrectinib eventually oc-
curs. Understanding the mechanisms of resistance could inform subse-
quent new personalized therapeutic options in these patients (pts).
Methods: Blood samples were collected at baseline and at time of pro-
gression from most pts in the NTRK+ and ROS1+ populations enrolled
in STARTRK-2 (NCT02568267). ese were tested using the Foundation
Medicine FoundationOne Liquid NGS-based test that assesses base sub-
stitutions, indels and rearrangements from 324 genes (including ROS1
and NTRK1,2,3), as well as copy number alterations from select genes
using ctDNA extracted from the plasma of pts from pre-treatment and
following progression on entrectinib.
Results: Of the 54 pts withNTRK+ tumors, 29 had paired samples at base-
line and progression at data cut-o. 10 pts (35%) had a detectable NTRK
solvent front mutation at disease progression (NTRK1: n=5; NTRK3:
n=5); not detected in the pre-treatment sample. BRAF V600E and KRAS
G12D mutations were detected at progression from a pancreatic cancer
pt who had a partial response. Of the 53 pts with ROS1+ NSCLC, 18had
paired samples at baseline and progression at data cut-o. 4 CD74-ROS1
and 1 SLC34A2-ROS1 pts showed the emergence of an acquired ROS1
resistance mutation (G2032R and F2004C/I) at disease progression (28%);
both not present pre-treatment. 1NRAS Q61K mutation was detected at
the end of treatment collection sample from a pt who had a partial re-
sponse.
Conclusions: From blood analysis, acquired resistance mutations were
detected in 35% of NTRK+ solid tumor and 28% of the ROS1+ NSCLC
cohorts, all of which were mutations in the kinase domain of the onco-
genic driver. 1 additional pt from each cohort showed the emergence of a
mutation in an oncogene within the MAPK pathway. Resistance to entrec-
tinib can occur by multiple mechanisms; this should be studied in larger
cohorts.
1052
A Final Report of the Phase I/IB Study of the Smoothened/
Hedgehog Pathway inhibitor Sonidegib Combined with
Azacitidine in Relapsed or Refractory AML and MDS Patients
Raoul Tibes1,2; Heidi Kosiorek3; Amylou Dueck3,3; Jeanne Palmer3;
James Slack3; James Bogenberger3; Darci Zblewski3; William Hogan3;
Mark Litzow3; Ruben Mesa3; James Foran3; Aref Al-Kali3
1NYU Langone Health and Perlmutter Cancer Center, New York University
Medical School , New York City, United States
2NYU
3Mayo Clinic
Background: Despite the remarkable improved response rates and new
standard combining the BCL-2 inhibitor Venetoclax with hypometh-
ylating agents (HMAs) or Low-dose AraC (LDAC) in newly diagnosed
elderly AML patients, the outcome of HMA and Venetoclax relapsed
or refractory (R/R) AML and MDS patients remains dismal. We identi-
ed inhibition of Hedgehog pathway (HP) genes as a potential rational
combination to overcome a priori and acquired HMA resistance. e
smoothened (SMO)/ hedeghog pathway inhibitor glasdegib has recently
been approved with LDAC in newly diagnosed AML and glasdegib with
HMA in upfront treatment has shown activity. To date there is no study
combining a SMO inhibitor in R/R AML and MDS. Here we report the
nal results of the rst study combining the SMO inhibitor Sonidegib
(SON, LDE225) in combination with Azacitidine (AZA) in 35 patients
with R/R AML or MDS.
Results: In a Ph1 (3+3) dose escalation and Ph1B (expansion cohort)
study 10 and 25 pts respectively were treated both arms. DLTs occurred at
400mg SON consisting of COP elevation and the MTD of the SONAZA
combination was determined at 200mg SON daily and AZA 75mg/m2 for
7 days each cycle every 28 days at which level 1 pt had grade 3 vomiting
(possibly related) and a 2nd pt had grade 3 fatigue (probably related).
Of 28 pts evaluated at the MTD dose level of 200 mg 2 pts had a CR and
MLFS, however 20 pts had no progression, only 2 pts progressed and 4
pts could not be assessed. At a median follow up of 8.7 ms, the overall
survival (OS) in the AML cohort was 7.6 ms with most of the pts having
failed prior HMA based treatment and/ or cytotoxic chemotherapy. e
6 ms OS was 50%. More remarkable, 1/3 of patients had a long response
ranging from 7-24 ms, despite having failed prior HMA.
Biomarker analysis of long-vs short responders is ongoing to identify pts
at chance of durable responses and will be presented at the meeting.
Conclusion: Combined SMO and HMA treatment in R/R AML and MDS
shows encouraging responses and biomarker stratication will help to
identify pts for a personalized medicine approach in hematology.
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2018
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2018
Epidemiology
Poster
998
The Direct Eect of Social Disparity on Head and Neck Cancer
Survival: Preliminary Results
Ahmed Bedir1; Dirk Vordermark1,2; Daniel Medenwald1,2
1University Hospital Halle (Saale), Department of Radiation Oncology, Health
Services Research Group, Halle (Saale), Deutschland
2University Hospital Halle (Saale), Department of Radiation Oncology, Halle
(Saale), Deutschland
Purpose: Despite recent clinical improvements of cancer treatment in
Germany, a marked dierence in cancer survival based on socio-economic
factors persists1. We aim to quantify the direct eect of socioeconomic
inequality on head and neck cancer survival, on the district-level,
independent of modiable external factors.
Methods: Patients diagnosed with head and neck cancer in1998-2014
from 10 German cancer registries (covering 32 million residents) were
included in our analysis. e Socioeconomic position of the patients
was determined using the German Index of Socioeconomic Deprivation
(GISD) assigned to German districts. e 5-year age-standardized relative
survival was calculated and stratied based on GISD quintiles. We used
mediation analysis to dierentiate between total eect of social inequality
and the amount meditated through treatment, stage at diagnosis, or num-
ber of hospital beds available at the respective district.
Results: e majority of the head and neck cancer patients lived in the
most deprived districts compared to the least deprived districts (11,203
vs 7,791). Although the mean age at diagnosis was lower in the deprived
districts, less patients were alive at the end of follow-up (40.1% vs. 53.4%).
80.0% of patients in the least deprived districts received radiotherapy
treatment compared to 61.1% of patients in the most deprived districts.
e 5-year age-standardized relative survival of patients living in the most
deprived districts compared to those living in the least deprived districts
was 60.0% vs 53.3% respectively.
Conclusions: Our preliminary results showed dierences in survival with
respect to socioeconomic position. Our descriptive analysis also suggests
a notable inequality when it comes to treatment received.
Reference:
1. Jansen, L., Eberle, A., Emrich, K., Gondos, A., Holleczek, B., Kajüter, H., Maier,
W., Nennecke, A., Pritzkuleit, R., & Brenner, H. (2014). Socioeconomic depri-
vation and cancer survival in Germany: An ecological analysis in 200 districts
in Germany. International Journal of Cancer, 134(12), 2951–2960.
Gastrointestinal (Colorectal) Cancer
Vorträge
1016
Letolimod vs Standard of Care (SOC) for Patients with
Metastatic Colorectal Cancer (mCRC) Responding to First-Line
Therapy: Results from IMPALA Trial
Dirk Arnold1; Depenbusch Reinhard2; Meinolf Karthaus3; Claus Bolling4;
Susanna Hegewisch-Becker5; Ramon Salazar6; Alberto Sobrero7;
Michel Ducreux8; Eric Van Cutsem9; Werner Schweithauer10;
Christophe Tournigand11; Daniela Schleif12; Mireille Starke12;
Matthias Baumann12; Erol Wiegert12; Manuel Schmidt12; David
Cunningham13
12. Medizinische Klinik, Onkologie mit Sektion Hämatologie Palliativmedizin,
Asklepios Tumorzentrum Hamburg AK Altona, Altona, Deutschland
2Onkologische Schwerpunktpraxis Gütersloh, Gütersloh, Deutschland
3Klinikum München Neuperlach, Klinik für Hämatologie und Onkologie
München, Deutschland
4Innere Medizin, Hämatologie/Internistische Onkologie, Palliativmedizin,
Medizinische Klinik I, Agalepsion Markus Krankenhaus, Frankfurt am Main ,
Deutschland
5Onkologische Schwerpunktpraxis, Hamburg, Deutschland
6Institut Català d‘Oncologia Hospital Duran i Reynals, Barcelona, Spanien
7IST-Istituto Nazionale per la Ricerca sul Cancro, Department of Medical
Oncology, IRCCS AOU San Martino -, Genova, Italien
8Medical Oncology, Gustave Roussy - Cancer Campus, Villejuif, Frankreich
9Digestive Oncology, University Hopitals Gasthuisberg Leuven and KU Leuven,
Leuven, Belgien
10Int.Med.I & CCC, Vienna General Hospital (AKH) - Medizinische Universität
Wien, Wien, Österreich
11Medical Oncology, Hôpital Henri Mondor, Créteil, Frankreich
12Mologen AG, Berlin, Deutschland, 13Royal Marsden NHS Foundation Trust/The
Institute of Cancer Research, Department of Medicine, Sutton, United Kingdom
Purpose: e TLR9 agonist letolimod broadly activates the innate and
adaptive immune system. Letolimod was evaluated in this phase 3 trial as
switch maintenance treatment in patients with mCRC who have respond-
ed to rst- line therapy.
Methods: e international, multicenter, open-label phase 3 IMPALA
trial was conducted including the AIO, TTD and GERCOR cooperative
groups. e study recruited 549 patients across 8 European countries
including 191 patients from German sites. Patients with an objective re-
sponse to rst-line induction therapy (5FU/FA or CAPE, plus OX or IRI,
alone or plus antiVEGF or antiEGFR) were randomized to receive either
letolimod monotherapy (experimental arm) or local SOC (control arm).
Aer rst progression, patients started re-induction therapy, with those in
the experimental arm continuing letolimod on top.
Results: Demographics and baseline characteristics were well balanced
between the study arms. Median duration of follow up was 35 months.
e primary endpoint overall survival (OS) was not met: median OS was
22.0 in the letolimod and 21.9 months in the control group (p=0.2765;
HR=1.12; 95% CI 0.91 - 1.38). Progression free survival, event-free rates,
pre-dened sub-group analyses including molecular and immunological
parameters for OS did also not indicate a benet. In comparison with the
control arm treatment with letolimod was generally well tolerated. Grade
3, 4 and 5 toxicities rates were 6.3, 1.9 and 0%, respectively and no new
safety signals or autoimmune events were identied while immune activa-
tion was conrmed in peripheral blood.
Conclusions: Letolimod did not show superiority to SOC as a single
agent maintenance treatment in patients with mCRC. Limited add-on
toxicity conrmed the favorable safety and tolerability prole of letoli-
mod. Hence, and given its mode of action, letolimod will be evaluated in
combination with other anti-cancer immunotherapies.
Reference:
1. Clinical trial identication NCT02077868
Disclosure Statement: e IMPALA study was sponsored by Mologen AG
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2018
Index
2018
Poster
897
Role of Intensied Radiochemotherapy for Older Patients
with Locally Advanced Rectal Cancer
Marko Kornmann1; Silvia Sander2; Doris Henne-Bruns1; Karl-Heinrich Link3
1Klinik für Allgemein- und Viszeralchirurgie, Universiätsklinikum Ulm, Ulm,
Deutschland
2Institut für Epidemiologie und Medizinische Biometrie, Universität Ulm, Ulm,
Deutschland
3Klinik für Chirurgie, Asklepios Paulinen Klinik Wiesbaden, Wiesbaden,
Deutschland
Purpose: e benet of adjuvant/neoadjuvant chemotherapy in combina-
tion with radiation for rectal cancer with regard to survival is negligible,
especially for older patients (pts). 5-uorouracil (5-FU) alone or in com-
bination with folinic acid (FA), oral capecitabine or an intensied therapy
using oxaliplatin are presently used. e aim of the present retrospective
evaluation was to compare the oncologic outcome of rectal cancer pts with
regard to adjuvant treatment and age.
Methods: Data of pts from the randomized phase-III FOGT-2 trial (1)
were updated and analyzed with regard to age, under 70 years termed
younger versus ≥ 70 years termed older.
Results: Out of the 796 pts included 140 were older (17.6%). Overall
257 pts displayed toxicity grade III/IV (32.3%), 217 (33.1%) occurred in
younger and 40 (28.6%) in older pts, respectively. Modulated treatment
increase toxicity in younger and older pts. 5-FU alone resulted in younger
and older pts in 35.2% (82/233) and 40.8% (20/49), respectively, in dis-
continuation of treatment, while modulated 5-FU had this eect in 36.9%
(156/423) and 44.0% (40/91), respectively. 8-year overall survival (8-y OS)
was 50.7% (95% CI: 43.1-57.8; n=282) for 5-FU alone and 52.3% (46.5-
57.9; n=514) for modulated 5-FU, respectively. 8-y OS was 52.8% (95%
CI: 44.8-60.2; n=233) for 5-FU alone and 55.9% (49.6-61.8; n=423) for
modulated 5-FU, respectively, in younger pts. Interestingly 8-y OS for old-
er pts was 41.4% (95% CI: 22.2-59.6; n=49) for 5-FU alone, but only 33.6%
(18.3-49.7; n=91) for modulated 5-FU.
Conclusions: In pts with rectal cancer under the age of 70 5-FU modu-
lation also in combination with radiation seems to increase the benet
in analogy to adjuvant treatment of colon cancer. Modulation of 5-FU in
combination with radiation seems to rather decrease outcome in pts ≥ 70
years and therefore should be avoided.
Reference:
1. Kornmann M et al. Br J Cancer 2010;103:1163-72.
Disclosure Statement: No conicts of interest.
901
Drivers of Secondary Resistance to Anti-Egfr Therapy in
Metastatic Colorectal Cancer
Soha Noseir1; Stephan Hahn2; Abdelouahid Maghnouj2;
Swetlana Ladigan2
1Zentrum für Klinische Forschung (ZKF) , Gastroenterologische Onkologie
(MGO), Bochum, Deutschland
2Universitätsklinikum Knappschaftskrankenhaus Bochum, Department of
Internal Medicine, Bochum, Deutschland
Purpose: Secondary Resistance (SR) evolves in virtually all metastatic col-
orectal cancers (mCRC) treated with anti-EGFR targeting drugs such as
Cetuximab (Cmab). Yet, SR patient-derived xenogra (pdx) models are
largely lacking. Here, we established eight SR pdx models through chron-
ic Cmab treatment of drug-sensitive mCRC pdx. All pdx models were
initially wild-type for KRAS, NRAS, PI3K and BRAF genes. Global gene
expression analyses identied widespread transcriptional reprograming
with many genes. Among the highly dysregulated genes, broblast growth
factors FGF13, FGF19, FGF20, and insulin-like growth factor IGF2 stood
out as potential drivers of SR through upregulation of RTK signaling.
Methods: Functional molecular analyses of these factors were performed
using lentiviral vector mediating gene transduction. Cell viability, prolif-
eration assays and western blot (WB) analyses were applied to assess the
molecular functionality of FGFs and IGF2-ligands in vitro. Finally, trans-
genic cell lines were injected into nude mice to test their therapeutic re-
sponse towards Cmab treatment.
Results: Stable lentiviral overexpression of FGF13 and IGF2 in drug-
sensitive cell lines and pdx models triggered SR both in vitro and in
vivo. WB analyses showed that FGF13 and IGF2 overexpression induced
phosphorylation of pAKT, pS6, and pERK. Conversely, knockdown of
FGF13 and IGF2 in a cell line with high endogenous IGF2 expression
improved Cmab sensitivity. Lastly, when subjecting a Cmab SR pdx model
with high endogenous overexpression of FGF13 and FGF19 to a Pan-FGF
inhibitor (LY2874455), we observed a conversion of the SR into partial
response.
Conclusions: Taken together, these results support a role of IGF2 and
FGFs as candidate proteins conferring SR in an autocrine fashion in the
setting of KRAS wild-type mCRC under chronic anti-EGFR treatment.
Importantly, these results also suggest that potential combination thera-
pies of Cmab and an IGF2 or FGF inhibitor could prevent establishment
of SR and oer new treatment opportunities for patients with SR mCRC.
1019
Noninferiority on Overall Survival of Every-2-Weeks vs Weekly
Schedule of Cetuximab for First-Line Treatment of RAS Wild-
Type Metastatic Colorectal Cancer
Stefan Kasper-Virchow1; Ann-LII Cheng2; Friedrich Overkamp3;
Magali Rouyer4; Caroline Foch5; Francois-Xavier Lamy5; Regina Esser5;
Diethelm Messinger6; Vivien Rothe6; Wenfeng Chen7; Thomas Brodowicz8;
Christoph Zielinski9
1University Hospital Essen, West German Cancer Centre, Essen, Deutschland
2National Taiwan University Cancer Center, Taipei City, Taiwan
3Oncologianova GmbH, Recklinghausen, Deutschland
4Bordeaux Pharmacoepi BPE, INSERM CIC 1401, University of Bordeaux,
Bordeaux, Frankreich
5Merck KGaA, Darmstadt, Deutschland
6Prometris GmbH, Mannheim, Deutschland
7Merck Serono, Shanghai, China
8General Hospital, Medical University of Vienna, Department of Medical
Oncology, Internal Medicine, Vienna, Österreich
9Vienna General Hospital and Medical University of Vienna, Comprehensive
Cancer Center, Vienna, Österreich
Purpose: Cetuximab (CET) in combination with chemotherapy (CT) is
approved for a once-weekly (q1w) schedule at an initial dose of 400 mg/m²,
followed by weekly doses of 250 mg/m², in patients with RAS wild-type
(wt) metastatic colorectal cancer (mCRC). In clinical practice, an o-label
schedule of CET 500 mg/m2 every-2-weeks (q2w) is used. is pooled
analysis of patient-level data (PLD) aimed to test the noninferiority of the
q2w vs q1w schedule on overall survival (OS).
Methods: All post-authorization studies with PLD available to marketing
authorization holder, in patients with RAS wt mCRC who received 1st-
line treatment with CET q1w or q2w in combination with CT from 2007
to 2018 were included: 2 non-interventional studies (NIS) and 3 clinical
trials. Patients were categorized as q1w or q2w according to CET schedule
planned at initiation. OS was assessed from CET initiation until all-cause
death and censored at last date known to be alive. Noninferiority of the
q2w vs q1w schedule was tested with a hazard ratio (HR) margin of 1.25
using a Cox proportional hazards regression model. Dierences in base-
line characteristics were accounted for with inverse probability of treat-
ment weighting (IPTW) based on a propensity score.
Results: 763 and 554 patients were included in the q1w and q2w groups,
respectively. Median (Q1-Q3) age in years was 66 (57-73) for q1w and
60 (53-69) for q2w. Liver-limited disease concerned 42.6% of patients for
q1w and 37.9% for q2w. A baseline ECOG Performance Status of 0-1 was
reported in 81.8% of q1w and 90.6% of q2w patients. FOLFIRI was most
frequently used in combination with q1w (49.4%) and FOLFOX with q2w
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2018
Index
2018
(59.2%). HRs for OS were in favor of q2w: 0.83 (95% CI, 0.71-0.96) and
0.73 (95% CI, 0.61-0.88) when restricted to NIS. Progression-free survival
and response rate support OS results.
Conclusions: is pooled analysis conrmed the noninferiority of CET
q2w vs q1w. Results suggest an improved OS with the q2w schedule.
Disclosure Statement: Previously presented at ESMO 2019, FPN 584P, Kasper et
al. Reused with permission. Wording adapted to match word count.
Gastrointestinal (Noncolorectal) Cancer
Vorträge
882
Atezolizumab (ATEZO) + Bevacizumab (BEV) vs Sorafenib
(SOR) in Patients (PTS) with Unresectable Hepatocellular
Carcinoma (HCC): Phase 3 Results from Imbrave150
Peter R. Galle1; Ann-LII Cheng2; Shukui Qin3; Masafumi Ikeda4; Michel
Ducreux5; Andrew Zhu6; Tae-You Kim7; Masatoshi Kudo8; Valeriy Breder9;
Philippe Merle10; Ahmed Kaseb11; Daneng LI12; Wendy Verret13; Derek Xu14;
Sairy Hernandez13; Juan Liu14; Hui Shao15; Sohail Mulla13; Hy Lim16; Richard
Finn17
1I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz,
Deutschland
2National Taiwan University Cancer Center, National Taiwan University Hospital,
Taipeh, Taiwan
3Peoples Liberation Army Cancer Center
4National Cancer Center Hospital East, Kashiwa, Japan
5Gustave Roussy Cancer Center, Villejuif, Frankreich
6Massachusetts General Hospital Cancer Center, Harvard Medical School,
Boston, United States
7Seoul National University College of Medicine, Seoul,
8Kindai University Faculty of Medicine, Osaka, Japan
9N.N. Blokhin Russian Cancer Research Center, Moscow, Russland
10University Hospital La Croix-Rousse, , Lyon, Frankreich
11The University of Texas MD Anderson Cancer Center, Houston, United States
12City of Hope Comprehensive Cancer Center and Beckman Research Institute,
Duarte, United States
13Genentech Inc., South San Francisco, United States
14Roche Product Development, Shanghai, China
15F. Homann-La Roche, Beijing, China
16Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
17Jonsson Comprehensive Cancer Center, Geen School of Medicine at UCLA,
Los Angeles, United States
Purpose: Ph 1b data has shown promising ecacy and safety for Atezo +
Bev in unresectable HCC pts who have not received prior systemic ther-
apy. We report the primary analysis data from the Ph 3 IMbrave150 trial
comparing Atezo + Bev vs Sor in this patient population.
Methods: IMbrave150 (NCT03434379) enrolled systemic treatment (tx)-
naïve pts with unresectable HCC. Pts were randomised 2:1 to receive
either Atezo 1200 mg IV q3w + Bev 15 mg/kg IV q3w or Sor 400 mg
BID until unacceptable toxicity or loss of clinical benet per investigator.
Coprimary endpoints were OS and PFS by independent review facility
(IRF) assessed RECIST 1.1. e key secondary endpoints IRF-ORR per
RECIST 1.1 and IRF ORR per HCC mRECIST were also part of the study
statistical hierarchy.
Results: e ITT population included 336 pts randomised to Atezo +
Bev and 165 randomised to Sor. Baseline demographics were well bal-
anced. With a median follow up of 8.6 mo, median OS was not estimable
(Atezo+Bev) vs 13.2 months (Sor). Median PFS was 6.8 months (95% CI,
5.7, 8.3) in Atezo + Bev vs 4.3 months (4.0, 5.6) in Sor. OS HR was 0.58
(0.42, 0.79; P = 0.0006) and PFS HR was 0.59 (0.47, 0.76; P < 0.0001) for
Atezo + Bev vs Sor. ORR was 27% vs 12% (P < 0.0001) per IRF RECIST
and 33% vs 13% (P < 0.0001) per IRF HCC mRECIST for Atezo + Bev vs
Sor, respectively. Results were consistent across clinical subgroups. Atezo
+ Bev delayed deterioration of quality of life vs Sor. Median tx duration
was 7.4 mo for Atezo, 6.9 for Bev and 2.8 for Sor. Gr 3-4 AEs occurred in
57% of pts receiving Atezo + Bev and 55% of pts receiving Sor. Gr 5 AEs
were seen in 5% and 6% of pts, respectively.
Conclusion: IMbrave150 demonstrated statistically signicant and clini-
cally meaningful improvement in both OS and PFS for Atezo + Bev vs Sor
in pts with unresectable HCC who have not received prior systemic thera-
py. e safety of Atezo + Bev is consistent with the known safety prole of
each agent, and no new safety signals were identied. Atezo + Bev has the
potential to be a practice changing tx in HCC.
Presented at ESMO Asia 2019, LBA #3, Cheng et al. Reused with per-
mission
916
Fight-202: A Phase 2 Study of Pemigatinib in Patients (PTS)
with Previously Treated Locally Advanced or Metastatic
Cholangiocarcinoma (CCA)
Arndt Vogel1; Vaibhav Sahai2; Antoine Hollebecque3; Gina Vaccaro4;
Davide Melisi5; Raed Al-Rajabi6; Andrew Scott Paulson7; Mitesh J Borad8;
David Gallinson9; Adrian G Murphy10; Do-Youn Oh11; Efrat Dotan12; Daniel
Catenacci13; Eric Van Cutsem14; Christine Lihou15; Huiling Zhen16; Luis
Féliz15; Ghassan Abou-Alfa17,18
1Hannover Medical School, Department of Gastroenterology, Hepatology and
Endocrinology, Hannover, Deutschland
2University of Michigan, Rogel Cancer Center, Ann Arbor, United States
3Gustave Roussy, Department of Adult Medicine, Villejuif, Frankreich
4Providence Cancer Center Oncology and Hematology Care Clinic, Hematology
Oncology, Portland, United States
5Università degli studi di Verona, Digestive Molecular Clinical Oncology
Research Unit, Department of Medicine, Verona, Italien
6University of Kansas Cancer Center, Department of Internal Medicine, Division
of Hematology/Oncology, Kansas City, United States
7Baylor University Medical Center, Baylor Charles A. Sammons Cancer Center,
Dallas, United States
8Mayo Clinic Cancer Center, Department of Internal Medicine, Phoenix, United
States
9Morristown Memorial Hospital, Carol Cancer Center - Department of
Hematology/Oncology, Morristown, United States
10Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive
Cancer Center, Department of Oncology, Baltimore, United States
11Seoul National University Hospital, Seoul National University College of
Medicine, Department of Internal Medicine, Seoul, South Korea
12Fox Chase Cancer Center, Department of Hematology/Oncology, Philadelphia,
United States
13University of Chicago Medicine, Department of Medicine, Chicago, United
States
14University Hospitals Gasthuisberg and KU Leuven Department of Digestive
Oncology, Leuven,
15Incyte Corporation, Clinical Development, Wilmington, United States
16Incyte Corporation, Biostatistics, Wilmington, United States
17Memorial Sloan Kettering Cancer Center, Department of Medicine, New York,
United States
18Weill Medical College at Cornell University, New York, United States
Purpose: Fibroblast growth factor receptor (FGFR) 2 alterations are
implicated in CCA. We present data from a phase 2, open label, single
arm study of pemigatinib, a potent, selective, oral FGFR1–3 inhibitor,
in pts with previously treated locally advanced or metastatic CCA
(NCT02924376).
Methods: Eligible adults had progressed aer ≥1 prior treatment and had
documented FGF/FGFR status. Pts assigned to cohorts A (FGFR2 rear-
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2018
rangements/fusions), B (other FGF/FGFR alterations), or C (no FGF/
FGFR alterations) received oral pemigatinib 13.5 mg QD (21-d cycle; 2
wks on, 1 wk o) until disease progression/unacceptable toxicity. Primary
endpoint was centrally conrmed objective response rate (ORR; cohort
A); secondary endpoints were ORR (cohorts B, A+B, and C); duration
of response (DOR), disease control rate (DCR), progression-free survival
(PFS), overall survival (OS); safety.
Results: At data cuto (Mar 22, 2019), 146 pts were enrolled (cohort A,
n=107; B, n=20; C, n=18; 1 pt undetermined). Median (range) age was
59 (26–78) y; 61% and 39% had 1 and ≥2 prior therapies. Fewer pts dis-
continued therapy in cohort A (71%) vs B and C (each 100%), most for
progressive disease (cohort A, 53%, B, 75%, C, 67%). ORR in cohort A was
35.5% (95% CI, 26.5%–45.4%), with 3 complete responses; median (m)
DOR was 7.5 (95% CI, 5.7–14.5) months (mo), DCR was 82% (95% CI,
74%–89%), mPFS and mOS were 6.9 (95% CI, 6.2–9.6) and 21.1 (14.8–not
reached) mo (OS not mature at cuto). In cohorts B and C, no patient
achieved a response. Overall, most common adverse events (AEs) were
hyperphosphatemia (60%; grade ≥3, 0%), alopecia (49%; 0%), diarrhea
(47%; 3%), fatigue (42%; 5%), nail toxicities (42%; 2%), and dysgeusia
(40%; 0%). Hyperphosphatemia was managed with diet modications,
phosphate binders, if needed; diuretics or dose reductions/interruptions.
Discontinuation, dose reduction and interruption due to AEs occurred in
9%, 14% and 42% of pts, respectively.
Conclusions: ese data support pemigatinib as a potential treatment
option for previously treated pts with CCA harboring FGFR2 gene rear-
rangements/fusions.
Poster
898
Characterization of the Immune Inltrate and its Prognostic
Value in Highly Proliferative Gastroenteropancreatic
Neuroendocrine Neoplasms (GEPNEN)
Vivian Katrin Rosery1,2; Phyllis Cheung1,3,4; Konstantinos Savvatakis1,3,4;
Martin Stuschke5; Andreas Paul6; Stefan Kasper2; Martin Schuler2,3;
Henning Reis7; Jens Siveke1,2,3,4
1Institute for Developmental Cancer Therapeutics, West German Cancer Center,
University Hospital Essen, Essen, Deutschland
2Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, Essen, Deutschland
3German Cancer Consortium (DKTK, partner site University Hospital Essen),
Essen, Deutschland
4German Cancer Research Center (DKFZ), Heidelberg, Deutschland
5Department of Radiotherapy, West German Cancer Center, University Hospital
Essen, Essen, Deutschland
6General, Visceral and Transplantation Surgery, University Hospital Essen, Essen,
Deutschland
7Institute of Pathology, West German Cancer Center, University Hospital Essen,
Essen, Deutschland
Purpose: e tumor immune microenvironment plays a critical role for
the response to “immune checkpoint blockade” in several cancer types.
We aimed to characterize the immune inltrate of highly proliferative
GEP-NEN in order to explore the potential role of immunotherapeutic
approaches in this fatal disease.
Methods: We analyzed formalin-xed paran-embedded (FFPE)
samples from 37 patients diagnosed with highly proliferative GEP-NEN
(G3; Ki-67>20%). Samples were immunohistochemically stained for
the checkpoint molecules PD-L1 and PD-1, and the immune markers
CD8 and CD206. PD-L1 positivity was dened as a CPS ≥1. PD-1 was
quantied as the percentage of positive immune cells. CD206 and CD8
were quantied using Denies Soware®. For PD-1, CD206 and CD8 the
median levels served as cuto. Marker expression was correlated with
overall survival (OS) using the log-rank (Mantel-Cox) test. Multiplex
immunouorescence (IF) staining illustrated the spatial interaction of
PD-L1, PD-1 and CD8.
Results: PD-L1 was signicantly associated with improved median
OS: 15.6 months (mth) (CI 95%: 7.0; 24.2) vs 9.3 mth (CI 95%: 3.7; 15)
(p=0.028). CD206, CD8 and PD-1 alone had no signicant impact on
OS. Co-expression of PD-L1 and high PD-1 was associated with a me-
dian OS of 19.1 mth (CI 95%: 9.4; 28.7) vs 9.3 mth (CI 95%: 3.4; 15.2)
(p=0.009). Patients with triple positive tumors (PD-L1, high PD-1, high
CD8) showed the longest median OS of 20.6 mth (CI 95%: 15.1; 26.1)
vs 10 mth (CI 95%: 5.4; 14.6) (p=0.002). IF illustrated the co-expression
of PD-1 and CD8 on cytotoxic T cells and a strong interaction between
PD1+CD8+ lymphocytes and PD-L1 on immune and tumor cells.
Conclusions: PD-1/PD-L1 co-expression had a stronger prognostic value
than CD8+ T cell inltrate alone, but simultaneous expression of these
three markers showed strongest prognostic relevance. Our data support
clinical studies of immunotherapy in highly proliferative GEP-NEN.
Disclosure Statement: e authors declare no conict of interest.
918
Maintenance Therapy with FOLFIRI after FOLFIRINOX for
Advanced Pancreatic Ductal Adenocarcinoma:
A Retrospective Single Center Analysis
Caspar Franck1; Ali Canbay1; Peter Malfertheiner1; Marino Venerito1
1Klinik für Gastroenterologie, Hepatologie und Infektiologie,
Universitätsklinikum Magdeburg, Magdeburg, Deutschland
Purpose: Patients with pancreatic ductal adenocarcinoma (PDA) receiv-
ing FOLFIRINOX oen develop oxaliplatin-induced polyneuropathy,
which limits the continuation of this therapy. We evaluated the ecacy
and safety of FOLFIRI maintenance treatment aer FOLFIRINOX induc-
tion in a retrospective single center study.
Methods: Patients with advanced PDA treated with FOLFIRI as main-
tenance therapy aer achieving disease control under FOLFIRINOX ac-
cording to the local operating procedure between 2011 and 2016 were
identied. Medical records of this group were evaluated retrospectively.
Results: Overall, 22 patients with PDA were treated with FOLFIRI (mean
age 59 years, 55 % female, 45 % male). Before receiving FOLFIRI all pa-
tients were treated with FOLFIRINOX for a median of 4 months. e me-
dian progression free survival (PFS) under FOLFIRI maintenance therapy
was 8 months. Side eects grade 3 - 4 (CTCAE v4.0) were observed in
18 % of patients receiving FOLFIRI. Considering together FOLFIRINOX
induction and subsequent FOLFIRI maintenance therapy, the median PFS
was 11 months. e median overall survival (OS) from the beginning of
palliative treatment was estimated at 46 months.
Conclusions: In the selected group of PDA patients achieving disease
control with FOLFIRINOX, FOLFIRI maintenance therapy was feasible,
safe and eective, with some patients achieving long-term disease stabi-
lization.
Disclosure Statement: M.V. has served as a speaker, a consultant or an advisory
board member for Lilly, Bristol-Myers Squibb, MSD, Merck Serono, Bayer vital,
Amgen, Nordic Pharma, Ipsen and Celgene. P.M. has served as a speaker for
Abbott Laboratories, Allergan, Alfasigma, Bayer, Biocodex, AstraZeneca, Falk
Pharma and Takeda. A.C. and C.F. have nothing to declare.
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971
Top Ten Research Priorities for the Treatment of Pancreatic
Cancer - Results of the Priority Setting Partnership Pancreatic
Cancer Treatment
Rosa Klotz1,2; Colette Dörr-Harim2; Azaz Ahmed3; Christine Tjaden1;
Markus K. Diener1,2; Thilo Hackert1; André L. Mihaljevic1,2
1Department of General, Visceral and Transplantation Surgery, Heidelberg
University Hospital, Heidelberg, Deutschland
2Study Centre of the German Surgical Society (SDGC), Heidelberg University
Hospital, Heidelberg, Deutschland
3Medical oncology, National Center for Tumor Diseases, University Hospital
Heidelberg, Heidelberg, Deutschland
Purpose: Pancreatic cancer (PC) is the fourth leading cause of cancer
deaths in Europe 1. Research is thus urgently needed. However, a mismatch
exists between research questions considered important by researchers
hand and those important to patients, carers, and health-care profession-
als2. In order to address this shortcoming a Priority Setting Partnerships
(PSPs) brings patients, carers and clinicians together to identify and prior-
itise unanswered questions that they agree are the most important.
Methods: A steering group consisting of an equal number of patients and
health-care professionals was established to decide on all aspects of the
PSP jointly. A modied nominal group method established by the James
Lind Alliance was used to involve patients, carers, members of patient
support groups, and health-care professionals. Between 2017-2019 open
research questions were identied and prioritized in two national-wide
surveys. Final prioritization of the remaining research questions was done
in a face-to-face consensus conference.
Results: In the rst survey from August to November 2017, >500 research
questions were obtained (52.1% patients). More uncertainties were added
aer screening current guidelines. Aer removal of duplicates and out of
scope questions, suggestions were collated to indicative questions and ver-
ied as unanswered in the research literature. e remaining uncertainties
were listed in the second survey for interim prioritization accomplished
from June to September 2019 (50.7% patients) to rank the top ten research
priority questions. From the 21 questions that received the most repre-
sentative votes, ten research priorities were agreed upon. e nal top 10
research questions will be presented at the Krebskongress 2020.
Conclusions: e identied top ten priorities for PC treatment provide an
important basis future researcher and funding bodies.
References:
1. Ferlay J, et al.. Eur J Cancer. 2018;103:356–87.
2. Crowe S, et al.. Res Involv Engagem. 2015;1:2
Disclosure Statement: e authors report not conicts of interest.
981
Obesity and Pancreatic Ductal Adenocarcinoma (PDAC): A
Matched-Pair Survival Analysis
Patrick Téoule; Nuh Rahbari; Christoph Reißfelder; Emrullah Birgin
Chirurgische Klinik, Universitätsklinikum Mannheim, Mannheim, Deutschland
Purpose: Incidence of morbid obesity is increasing in western world. Ep-
idemiological data show that obesity has an impact on overall survival
(OS) of many tumors and postoperative complication rates1,2. is study
evaluates the inuence of obesity on OS in patients with PDAC.
Methods: From a prospective database, we retrospectively evaluated all
patients who underwent pancreatic resection for PDAC (1997-2018).
Matched pairs (1:1) were generated according to the following predened
match criteria: age, gender and ASA. Only full matches were accepted.
Primary endpoint was the OS dierence of patients with and without
obesity. Obesity was dened according to the WHO criteria as BMI >
30 kg/m2. Secondary endpoints were intra- and postoperative outcomes,
pathological characteristics and adjuvant chemotherapy. Survival analysis
was done by using Kaplan-Meier and uni- and multivariate analysis were
performed for comparison between groups.
Results: Out of 553 patients a total of 76 fully matched pairs were gener-
ated. Obese patients had a mean BMI-level of 33 compared to 25 kg/m2
in patients without obesity. All patients had ASA-status ≤III. Patients with
obesity had a higher frequency of diabetes m. (49% vs. 30%, p=0.031) and
Clavien-Dindo grade >III was slightly higher (14% vs. 9%, p=0.182). 90-
day mortality rates were similar in both groups. 39 obese patients (57%)
received adjuvant chemotherapy compared to 30 (46%) (p=0.226). e
median OS was 19 months (12-29) in patients with and 21 months (12-26)
without obesity (P=0.99).
Conclusions: We could not observe an inuence of obesity on OS and
postoperative complications in patients with PDAC. erefore, pancreatic
surgery should not be withheld for obese patients.
References:
1. Watanabe, A. et al. Risk factors associated with surgical site infection in upper
and lower gastrointestinal surgery. Surg. Today 38, 404–412 (2008).
2. Bentrem, D. J. et al. Predictors of intensive care unit admission and related
outcome for patients aer pancreaticoduodenectomy. J. Gastrointest. Surg. 9,
1307–1312 (2005).
Disclosure Statement: -
985
Prognostic Value of Systemic Inammatory Response
Markers in Highly Proliferative Gastroenteropancreatic
Neuroendocrine Neoplasms GEPNEN
Vivian Katrin Rosery1,2; Phyllis Cheung2,3,4; Stephan Mika1;
Martin Stuschke5; Andreas Paul6; Henning Reis7; Jens Siveke1,2,3,4;
Martin Schuler1,3; Stefan Kasper1
1Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, Essen, Deutschland
2Institute for Developmental Cancer Therapeutics, West German Cancer Center,
University Hospital Essen, Essen, Deutschland
3German Cancer Consortium (DKTK, partner site University Hospital Essen),
Essen, Deutschland
4German Cancer Research Center (DKFZ), Heidelberg, Deutschland
5Department of Radiotherapy, West German Cancer Center, University Hospital
Essen, Essen, Deutschland
6General, Visceral and Transplantation Surgery, University Hospital Essen, Essen,
Deutschland
7Institute of Pathology, West German Cancer Center, University Hospital Essen,
Essen, Deutschland
Purpose: Chronic inammation plays a critical role in the development
and progression of cancer (1). Systemic inammatory response (SIR)
markers can be routinely assessed in clinical settings and are associated
with survival in several cancer entities (2). In this study, we evaluated the
prognostic value of pretreatment SIR markers in highly proliferative gas-
troenteropancreatic neuroendocrine neoplasms (GEP-NEN).
Methods: We established a database of 82 patients with highly prolifer-
ative GEP-NEN (G3; Ki-67>20%). SIR markers were retrospectively as-
sessed before start of any treatment (resection, radiation or chemothera-
py). Absolute blood cell count was applied. Cuto values were set as the
median of each marker. SIR markers such as the dierential blood count,
CRP, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte
ratio (LMR) and platelet-to-lymphocyte ratio (PLR) were correlated with
overall survival (OS) using the log-rank (Mantel-Cox) test and Cox pro-
portional hazard models.
Results: Median OS of the full cohort was 11 months (CI 95%: 9.7; 12.3
month). High blood lymphocyte counts were signicantly associated with
better OS: 13.1 vs 9.5 month (HR 0.58; CI 95%: 0.36; 0.95; p=0.03). e
median OS for patients with high NLR was 9.5 vs 13.1 months (HR 1.69;
CI 95%: 1.04; 2.75; p=0.035), for high LMR: 14 vs 7.4 months (HR 0.49;
CI 95%: 0.3; 0.8; p=0.004), for high PLR: 10 vs. 14 months (HR 1.67; CI
95%: 1.02; 2.73; p=0.04) and for high CRP: 7.6 vs 14.2 months (HR 1.85;
CI 95%: 1.14; 3.01; p=0.013).
Conclusions: Our data suggest a strong prognostic value of pretreatment
SIR biomarkers in highly proliferative GEP-NEN. Especially the absolute
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lymphocyte count could serve as a stratication factor for further treat-
ment studies in this disease.
References:
1. Grivennikov SI, Greten FR and Karin M (2010). Immunity, inammation, and
cancer. Cell 140(6): 883-899.
2. Ohno Y (2019). Role of systemic inammatory response markers in urological
malignancy. Int J Urol 26(1): 31-47.
Disclosure Statement: e authors declare no conict of interest.
999
Investigating the Impact of Extrahepatic Metastasis in
Patients with HCC: Does Location Matter?
Roman Klöckner1; Marie-Theres König1; Felix Hahn1; Christoph Düber1;
Peter R. Galle2; Aline Maehringer-Kunz1; Arndt Weinmann2,3
1Diagnostic and Interventional Radiology, University Medical Center Mainz,
Mainz, Deutschland
2University Medical Center Mainz, Department of Internal Medicine -
Hepatology, Mainz, Deutschland
3University Medical Center Mainz, Clinical Research Unit (CRU), Mainz,
Deutschland
Purpose: Extrahepatic metastatic disease (EMD) in patients with hepa-
tocellular carcinoma (HCC) leads to classication into advanced stage in
which systemic therapy is recommended. However, data on the prognos-
tic impact of EMD is rare, especially when taking into account the exact
location. erefore, aim of this study was to determine the prognostic
impact of EMD in general and according to dierent EMD sites using a
longitudinal approach.
Methods: As the work-up is still ongoing, so far 741 patients with HCC
treated between 01/2005-01/2019 were extracted from the clinical registry
of our tertiary referral center to reevaluate the impact of EMD. All cross
sectional imaging studies were re-reviewed by a board certied radiolo-
gist specialized in HCC-imaging to determine date and location of EMD
development. Locations were classied into 6 categories: lymph nodes,
peritoneum, lung, bone, adrenal gland, brain, and others. Furthermore,
the status of macrovascular invasion (MVI) was determined.
Results: Of the 741 patients, 41 patients could not be evaluated due to
concurrent malignant disease. Overall, 153/700 patients developed EMD:
73 (47.8%) patients presented with EMD synchronous to initial HCC di-
agnosis, 80 (52.2%) patients had metachronous EMD. Median OS aer
initial diagnosis was 15.8 months without and 10.9 months with EMD
(p<0.001). e most common metastatic sites were: lymph node (n=79),
lung (n=78), bone (n=37), peritoneum (n=30), adrenal gland (n=23), and
others (n=13). Residual median OS aer detection of lymph node, lung,
bone, peritoneal, adrenal, brain, and other metastases was 5.6, 5.1, 3.4, 4.3,
5.8, and 5.6 months respectively (p>0.05). Incidence of MVI in patients
with EMD was higher than in patients without EMD (p<0.001).
Conclusions: EMD had a signicant impact on OS. However, there was
no discernible dierence in OS between metastatic sites. erefore, un-
der systemic treatment, the exact site is rather of secondary importance
for OS. As EMD showed strong correlation with MVI, diagnosis of MVI
should prompt additional imaging.
Disclosures: None
1033
Optineurin Knockdown Reverses Cell Cycle Changes Induced
by Cisplatin in BRCA1 Mutated and Wild Type Pancreatic
Cancer Cells
Doaa M. Ali1; Viktor Tenev1,2; Michael Zepp1; Spiro Konstantinov2; Martin
Berger1
1German Cancer Research Institute, Heidelberg, Deutschland
2Medical University of Soa, Department of Pharmacology, Pharmacotherapy
and Toxicology, Soa, Bulgaria
Purpose: BRCA mutations have been associated with increased sensitiv-
ity to cisplatin in ovarian and breast cancers. Autophagy plays a role in
acquired chemotherapeutic resistance. Pancreatic ductal adenocarcino-
ma (PDAC) shows high levels of basal autophagy and PDAC cell lines
can harbor BRCA mutations. In the present work, the eect of cisplatin
was investigated in Capan1 cells, which harbor a BRCA2 mutation and in
Miapaca cells, which are BRCA wild type; this treatment was combined
with knockdown of the autophagy receptor optineurin (OPTN) for ob-
taining improved therapeutic outcome.
Methods: Proliferation was tested in Miapaca (BRCA2 wild type) and
Capan1 (BRCA2 mutated) cells by MTT-assay aer exposure to cispla-
tin. OPTN was knocked down by specic siRNA (30 pM). Aer 48 h, the
eect on mRNA and protein expression levels was determined by qRT-
PCR and Western blot. e inuence on cell cycle distribution was
followed by FACS. Western blot was used to assess protein levels of p-P53,
and p-Chk 2.
Results: Capan1 cells were by 2 orders of magnitude more sensitive to
cisplatin than Miapaca cells (IC50 Capan: 0.06 µM compared to 6 µM in
Miapaca cells at 72 h). In Miapaca cells, cisplatin reduced the percent-
age of G1 phase cells by 56% and increased that of S-phase cells by 66%.
In Capan 1 cells, it reduced the G1 fraction by 41% and increased the S
fraction by 48%. Interestingly, these eects were almost normalized when
cisplatin was combined with knockdown of OPTN. A signicant increase
was observed in both cell lines in the expression of p-Chk 1, and p-P53.
Conclusions: Cisplatin showed a higher sensitivity in the PDAC cell line
containing a BRCA mutation. Knockdown of OPTN lead to normalizing
the eect of cisplatin on cell cycle in both cell lines.
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Genito-urinary Cancer, including Prostate Cancer
Poster
873
Sarcopenia Assessments as Predictors of Overall Survival in
Patients with Metastatic Renal Cell Carcinoma
Luca Kümmerl1; Wladimir Lesyuk2; Peter J. Goebell1; Andreas Kahlmeyer1
1Universitätsklinikum Erlangen, Urologische und Kinderurologische Klinik,
Erlangen, Deutschland
2Universitätsklinikum Erlangen, Radiologisches Institut, Erlangen, Deutschland
Purpose: Sarcopenia can be an important prognostic marker in tumor
patients receiving systemic therapy. However, measurement methods and
threshold values are not uniformly dened. e aim of this study is there-
fore to determine the prognostic value of dierent sarcopenia indices in
patients with metastatic renal cell carcinoma treated with TKI.
Methods: In 93 patients who received TKI therapy for metastatic renal
cell carcinoma, sarcopenia indices were determined based on CT imaging
before the start of therapy. Clinical progression parameters were recorded
prospectively. e correlation of sarcopenia parameters with overall sur-
vival was investigated as univariate and multivariate correlations, taking
into account the MSKCC score.
Results: e mean age at inclusion was 65.8 years (21-86). Median sur-
vival was 12.3 months. e total muscle cross-section at LWK-3 level was
112.9 cm² in women and 159.0 cm² in men.
As the denitions of sarcopenia dier considerably, 23-55% of the patients
were classied as having sarcopenia. In univariate and multivariate analy-
sis, indices based on total muscle area and indices based on psoas muscle
are signicantly associated with overall survival.
Conclusions: e determination of sarcopenia indices using routine CT
imaging can contribute to the prognosis estimation of patients under TKI
therapy with metastatic renal cell carcinoma. Indices based on the exact
determination of skeletal muscle area or psoas muscle area at LWK-3 are
independent prognostic markers.
958
A Phase III Study Testing the Role of Proactive Coaching on
Patient Reported Outcome in Advanced or Metastatic Renal
Cell Carcinoma Treated with Sunitinib or a Combination of
Axitinib + Checkpoint Inhibitor (CPI) in First Line Therapy
(Prepare)
Viktor Grünwald1; Philipp Ivanyi2; Lutz Jacobasch3; Mark-Oliver Zahn4;
Andreas Hübner5; Ludwig Fischer von Weikersthal6; Marinela Augustin7;
Berit Eberhardt8; Martin Mänz9
1Westdeutsches Tumorzentrum Essen, Universitätsklinikum Essen (AöR), Essen,
Deutschland
2Klinik für Hämatologie, Hämostaseologie, Onkologie u.
Stammzelltransplantation, Medizinische Hochschule Hannover (MHH),
Hannover, Deutschland
3BAG Gemeinschaftspraxis Hämatologie - Onkologie, Dresden, Deutschland
4MVZ Onkologische Kooperation Harz, Goslar, Deutschland
5Wissenschaftskontor Nord GmbH & Co KG, Rostock, Deutschland
6Praxis für Hämatologie und Internistische Onkologie, Klinikum St. Marien
Amberg, Amberg, Deutschland
7Klinik für Innere Medizin 5, Schwerpunkt Onkologie / Hämatologie,
Universitätsklinik der Paracelsus Medizinischen Privatuniversität, Nürnberg,
8Die Uronauten, Berlin,
9AIO-Studien gGmbH, Berlin, Deutschland
Purpose: PREPARE is an ongoing phase III clinical study that tests if
structured pre-emptive therapy management during sunitinib treatment
improves clinical outcome. Since the conception of the PREPARE study,
new mRCC treatment strategies using immune checkpoint inhibitors
(CPI) have emerged. Promising approaches include the combination of
CPIs with tyrosine kinase inhibitors (TKI) such as the recently approved
combinations of axitinib + avelumab or pembrolizmab. erapy manage-
ment in PREPARE aims to raise awareness, educate patients and imple-
ment preventive measures in routine practice. is principle is also very
relevant to the novel combinations and an adaptation of the procedures
within PREPARE will allow for the enrollment of patients treated with
axitinib + CPI.
It is hypothesized that this approach of proactive coaching of mRCC pa-
tients receiving 1st-line sunitinib or a combination of axitinib + CPI will
improve patients health-related quality of life and may improve patient
adherence to treatment and ultimately clinical outcome.
Methods: 430 patients will be randomized 1:1 between concomitant
coaching and standard of care. Nurses are trained in proactive Adverse
Drug Reaction (ADR) management in order to act as coaches and as such
collaborate closely with the investigators. Coaching aims at patient edu-
cation on ADRs, preventive measures, self-care and remedies, including
management of fatigue, diarrhea, stomatitis, skin toxicities and hyperten-
sion. Quality of life will be assessed as primary endpoint using FKSI-15.
Secondary outcome measures include ORR, progression-free survival,
overall survival, treatment duration and ADRs.
Results: Initiation of study sites started in January 2017 and is ongoing.
As of January 2020, 24 study sites have been initiated and 40 patients ran-
domized. Results will be published aer nalization of study.
Conclusions: PREPARE will shed further light on the value of proactive
management of TKI side eects as well as TKI-CPI combinations.
ClinicalTrials.gov Identier: NCT03013946
EudraCT No.: 2016‐000399‐28
980
Molecular Tumor Board for Metastatic Prostate Cancer in
Routine Clinical Practice
Franziska Beckert1; Cornelius Leopold1; Margitta Retz1; Robert Tauber1;
Philipp Jost2,3; Nicole Pfarr4; Matthias Heck1; Jürgen Gschwend1;
Lukas Lunger1
1Department of Urology, Rechts der Isar Medical Center, Technical University of
Munich, München, Deutschland
2Comprehensive Cancer Center Munich partner site TUM , Deutschland
3Medical Department III for Hematology and Oncology, Rechts der Isar Medical
Center, Technical University of Munich, München, Deutschland
4Department of Pathology, Rechts der Isar Medical Center, Technical University
of Munich, München, Deutschland
Purpose: Molecular stratication for targeted tumor therapy in metastatic
prostate cancer (PC) is not routinely implemented. Previous studies found
that PC cells frequently harbor aberrant cellular signaling pathways asso-
ciated with treatment response [1-3]. Here we present the data obtained
from PC patients analyzed by the Molecular Tumor Board (MTB) Techni-
cal University of Munich as a framework classifying genomic alterations
for cancer precision medicine in routine practice.
Methods: Key MTB inclusion criteria were conrmed metastatic PC with
one of the following items: patient age < 60 years, unusual metastasis pat-
tern, aggressive course of disease or last line tumor therapy. Fresh tumor/
metastasis biopsy material was processed. e Oncomine Comprehensive
Assay using next-generation sequencing was used to detect relevant sin-
gle-nucleotide variants, copy number variations, gene fusions and indels.
Microsatellite instability (MSI) and PDL-1 status was assessed by immu-
nohistochemistry. Process maps for MTB screening, inclusion, treatment
and follow-up were designed. A license for a secure web-based soware
platform created to support data capture for research was obtained and a
unique electronic case report form was designed [4].
Results: e routine MTB procedure was initiated in November 2019 and
a total of 17 PC patients were already included within two months: 10/17
(59%) patients showed clinically actionable mutations targeting pre-
dominantly the PI3K/Akt/mTOR. 6/17 (35%) patients had mutations in
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DNA-repair pathways and were eligible for PARP-inhibitor therapy. 1/17
(6%) positive PDL-1 status but no MSI were detected.
Conclusions: e initiation of advanced clinically integrative genomics
in metastatic PC is an important step to enhance the personalized cancer
therapy in routine practice.
References:
1. Mateo, J., et al., N Engl J Med, 2015
2. Robinson, D., et al., Cell, 2015
3. Mateo, J., et al., Ann Oncol, 2018
4. Harris, P.A., et al., J Biomed Inform, 2019
Disclosure Statement: e authors declare no conict of interest and have nothing
to disclose.
993
Depth of Response (DEPOR) Analysis and Correlation with
Clinical Outcomes from JAVELIN Renal 101
Martin H. Voss1; Robert J. Motzer2; Laurence Albiges3; Brian I. Rini4;
Manuela Schmidinger5; James Larkin6; John B.A.G. Haanen7;
Christian Kollmannsberger8; Matthew T. Campbell9; Sumanta K. Pal10;
Gwenaelle Gravis11; Michael B. Atkins12; Bo Huang13;
Aleksander Chudnovsky14; Alessandra DI Pietro15; Despina Thomaidou16;
Toni K. Choueiri17
1Jena University Hospital, Am Klinikum 1, Jena, Deutschland
2Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, United
States
3Institut Gustave Roussy, Maison du projet 39, rue Camille Desmoulins, Villejuif,
Frankreich
4Cleveland Clinic - Taussig Cancer Center, CA Building, 10201 Carnegie Avenue,
Cleveland, United States
5Medical University of Vienna, Klinik für Innere Medizin I, Klinische Abteilung für
Onkologie, Waehringer Guertel 18-20, Wien, Österreich
6The Royal Marsden NHS Foundation Trust, 203 Fulham Rd, Chelsea, London,
United Kingdom
7The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, Niederlande
8British Columbia Cancer Agency, 600 West 10th Ave, Vancouver, Kanada
9The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd.,
Houston, United States
10City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte,
United States
11Institut Paoli Calmettes, 232 boulevard de Sainte Marguerite, Marseille,
Frankreich
12Georgetown-Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd. NW,
Washington D.C., United States
13Pzer Inc, 280 Shennecossett Rd, Groton, United States
14Pzer Inc, 1 Portland St, Cambridge, United States
15Pzer SRL, Via Anna Maria Mozzoni, 12, Milano, Italien
16Pzer Hellas, Leof. Mesogeion 243, Neo Psichiko, Athens, Griechenland
17Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and
Brigham and Women’s Hospital, 450 Brookline Ave, Boston, United States
Purpose: e phase 3 JAVELIN Renal 101 trial (NCT02684006) demon-
strated signicantly improved progression-free survival (PFS) in patients
(pts) with advanced renal cell carcinoma (aRCC) treated with avelumab +
axitinib (A+Ax) vs sunitinib (S) (HR, 0.69; 95% CI, 0.56, 0.84; P<0.001).1
We report on the correlation of PFS with DepOR at early imaging time-
points.2
Methods: Data from all pts were analyzed based on blinded independent
central review per RECIST 1.1. Tumor shrinkage or growth was catego-
rized by best % change in target lesions on imaging obtained up to 13 wk.
e landmark analysis included pts without progressive disease and who
had not died at or prior to 13 wk aer randomization. PFS was analyzed
for each category. A Cox multivariate landmark analysis was conducted
for PFS in the A+Ax arm with DepOR as a continuous variable.
Results: Results are reported based on the rst interim analysis, with a
minimum follow-up of 6.0 mo. Within shrinkage categories ≥0 – <30%,
≥30 – <60%, and ≥60%, median PFS (95% CI) in the A+Ax arm was 16.6
mo (13.8, not estimable [NE]), NE (13.3, NE), and NE (NE) vs 16.7 mo
(11.1, NE), 13.9 mo (9.1, NE), and NE (6.2, NE) in the S arm, respectively.
e 12-mo PFS rates (95% CI) in the A+Ax arm were 63.2% (52.5, 72.2),
68.4% (58.9, 76.1), and 85.2% (60.2, 95.1) vs 57.0% (47.6, 65.3), 60.3%
(39.9, 75.7), and 66.7% (28.2, 87.8) in the S arm, respectively. In the tumor
growth category >0 – <20%, median PFS in the A+Ax arm was 5.7 mo
(4.2, NE) vs 9.5 mo (5.6, 17.3) in the S arm; the 12-mo PFS rate (95% CI)
was 27.0% (7.6, 51.3) vs 42.0% (18.8, 63.7). Aer adjusting for prognostic
covariates, Cox multivariate analyses showed a meaningful association
between DepOR and PFS in the A+Ax arm, consistent with the results in
each shrinkage category.
Discussion: Greater tumor shrinkage at early imaging timepoints was
associated with longer PFS in JAVELIN Renal 101.
Conclusions: DepOR could be a predictor of clinical outcomes in pts with
aRCC.
References:
1. Motzer, et al. N Engl J Med. 2019;380:1103-15.
2. Prior submission: ASCO-GU 2020 (#286971).
Funding: Pzer and Merck KGaA, Darmstadt, Germany
1023
Race IT-Preoperative Radiation Therapy Before Radical
Cystectomy Combined with Immunotherapy in Locally
Advanced Urothelial Carcinoma of the Bladder
Franziska Beckert1; Margitta Retz1; Lukas Lunger1; Phillip Maisch1;
Claus Rödel2; Florestan Koll1; Andreas Sauter3; Anna Seitz4; Hubert Kübler4;
Michael Flentje5; Felix Chun6; Stephanie Combs7; Kilian Schiller7;
Jürgen Gschwend1; Sebastian Schmid1
1Department of Urology, Rechts der Isar Medical Center, Technical University of
Munich, München, Deutschland
2Department of Radiation Oncology, Johann Wolfgang Goethe-Universität,
Frankfurt, Deutschland
3Department of Radiology, Rechts der Isar Medical Center, Technical University
Munich, München, Deutschland
4Department of Urology, Universitätsklinikum Würzburg, Würzburg,
Deutschland
5Department of Radiation Oncology, Universitätsklinikum Würzburg, Würzburg,
Deutschland
6Department of Urology, Johann Wolfgang Goethe-Universität, Frankfurt,
Deutschland
7Department of Radiation Oncology, Rechts der Isar Medical Center, Technical
University Munich, München, Deutschland
Purpose: Patients with locally advanced bladder cancer have a poor prog-
nosis despite radical surgical therapy.[1] Anti-PD1/PDL1-based immuno-
therapies have shown activity in metastatic urothelial cancer. Preliminary
data on neoadjuvant immunotherapy in muscle invasive bladder cancer
demonstrated high antitumor activity. Early data suggest a synergistic
eect of radiation and immunotherapy. erefore we designed a trial to
evaluate feasibility, safety and ecacy of neoadjuvant radio-immunother-
apy before radical cystectomy in this cohort.
Methods: In this prospective, multicenter, phase II IIT- trial, patients
(n=33) are treated with Nivolumab 240 mg q2w for 4 cycles with si-
multaneous radiotherapy of the pelvis with 50.4 Gy. Aer the treatment
phase a radical cystectomy is performed with a postoperative follow-up
phase. Main inclusion criteria are locally advanced (cT3/4 cN0/N+ cM0)
urothelial bladder cancer in patients, who are unt for neoadjuvant cis-
platin-based chemotherapy or refuse neoadjuvant chemotherapy. Main
exclusion criteria are metastatic disease, prior chemotherapy and pelvic
radiation.
Results: Since February 2019 11 patients were enrolled. A planned inter-
ims analysis regarding safety was performed with positive result.
Conclusions: Aer an inclusion of a third of the study population and a
planned interim analysis for safety, further patient recruitment will con-
tinue in January 2020.
Clinical trial information: NCT03529890
Reference:
1. Hautmann, R.E., et al., J Urol, 2006. 176(2): p. 486-92.
Disclosure Statement: SCS received travel grants from Astellas, Janssen-Cilag, No-
vartis and Bristol-Myers Squibb (BMS). MR received consultancy honoraria from
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Index
2018
Bayer, BMS, Ipsen Pharma, Janssen Cilag, MSD, Novartis, Pierre Fabre, Pzer and
Roche and JEG from Bayer, BMS, MSD, Novartis, Pierre Fabre, Pzer and Roche.
1037
A Randomized Phase II Study of Nivolumab Plus Ipilimumab
Versus Standard of Care in Previously Untreated and
Advanced Non-Clear Cell Renal Cell Carcinoma (Suniforecast)
Marit Ahrens1; Bernard Escudier2; Ekaterini Boleti3; Marc-Oliver Grimm4;
Marine Gross Goupil5; Pilippe Barthélémy6; Gwenaelle Gravis7; Jens
Bedeke8; Philipp Ivanyi9; Andrej Panic10; Stefanie Zschäbitz11; Sylvie
Negrier12; Begona Mellado13; Anika Biel14; Tom Wadell15; Jose Pablo
Maroto16; Margitta Retz17; Martin Boegemann18; Sylvie Rottey19; John
Haanen20; Sjoukje Oosting21; Daniel Castellano22; Arndt Hartmann23;
Lothar Bergmann1
1Uniklinik Frankfurt, Med. Klinik II, Frankfurt, Deutschland
2Institut Gustave Roussy, Paris, Frankreich
3Royal Free London NHS Foundation Trust, London, United Kingdom
4Universitätsklinik Jena, Clinic for Urology, Jena, Deutschland
5Centre Hospitalier Universitaire, Bordeaux, Frankreich
6Les Hospitaux Universitaire de Strasbourg, Strasbourg, Frankreich
7Institut Paoli Calmettes, Clinic for Oncology, Marseille, Frankreich
8Universitätsklinik Tübingen, Clinic for Urology, Tübingen, Deutschland
9MHH Hannover, Med. Klink II, Hannover, Deutschland
10Universitätsklinik Essen, Clinic for Urology, Essen, Deutschland
11Universitätsklinik Heidelberg, National Center for Cancer (NCT), Heidelberg,
Deutschland
12Centre Leon Berard, Lyon, Frankreich
13Hospital Clinic de Barcelona, Clinic for Oncology, Barcelona, Spanien
14Universitätsklinik Düsseldorf, Clinic for Urology, Düsseldorf, Deutschland
15University of Manchester, Paterson Institute for Cancer Research, Manchester,
United Kingdom
16San Pau Hospital, Barcelona, Spanien
17Universitätsklinik Rechts der Isar, Clinical for Urology, München, Deutschland
18Universitätsklinik Münster, Clinic for Urology, Münster, Deutschland
19University Hospital Gent, Gent, Belgien
20Netherlands Cancer Institute, Amsterdam, Niederlande
21University Medical Centre Groningen, Groningen, Niederlande
22Hospital Universitario 12 de Octubre, Clinic for Oncology, Madrid, Spanien
23Universitätsklinik Erlangen, Institut für Pathologie, Erlangen, Deutschland
Purpose: Non-clear cell renal cell carcinomas (nccRCC) are heteroge-
neous tumors accounting for approximately 25% of RCC patients (pts).
Since most clinical trials focus on clear-cell RCC (ccRCC), data on treat-
ment strategies for nccRCC are limited. e combination of Nivolumab
and Ipilimumab has recently been approved for treatment in RCC show-
ing a signicant improvement in overall survival (OS), progression free
survival (PFS) and overall response (ORR) in intermediate and high-risk
pts. compared to sunitinib. Currently retrospective analyses have also
shown promising results for this combination in nccRCC patients.
Methods: In this prospective randomized phase-II multicenter trial pts
with advanced or metastatic nccRCC with no prior systemic therapy are
eligible. Other key inclusion criteria are: available tumor tissue, Karnofsky
>70% and measurable disease per RECIST 1.1. All diagnoses are reviewed
by a central pathologist. e study plans to randomize ~306 pts stratied
for papillary or non-papillary histology and by the International Metastat-
ic RCC Database Consortium (IMDC) risk score. Pts will be randomized
1:1 to either i) Nivolumab 3mg/kg intravenously (IV) plus Ipilimumab
1mg/kg IV every 3 weeks for 4 doses followed by Nivolumab xed dose
240mg IV every 2 weeks or ii) standard of care according to the approved
schedule. Treatment will be discontinued in case of unacceptable toxicity
or withdrawal of informed consent. Pts may continue treatment beyond
progression, if clinical benet is achieved and treatment is well tolerat-
ed. Primary endpoint is the OS rate at 12 months. Secondary endpoints
include OS rate at 6 and 18 months, median OS, PFS, ORR and quality
of life. e trial is in progress and 111 pts have been randomized so far.
Clinical trial identication NCT03075423
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Geriatric Oncology
Poster
912
Immunoncology in Elderly Patients is Safe and Even
Successful
Michael Schroeder1,; U. Wieschermann; M. Heinsch; S. Theodoropoulou;
U. G. Grigoleit
1Helios St. Johannes Klinikum Duisburg, Hämatologie- Onkologie- Immunologie ,
Duisburg, Deutschland
Introduction: Immunoncology has became the fourth component in tu-
mour treatment and shows oen remarkable results in many tumour enti-
ties ( lung cancer, melanoma, head and neck tumours, renal and urotheli-
um carcinoma, SCC of the skin ). Side eects of immunoncology are quiet
dierent to chemotherapy, but we learned to manage these side eects.
Method: We report of 24 patients ( male: 19; female: 5) aged over 70
years ( range 70 – 92 years ), who entered our hospital between 10/2016
and 09/2019 for treatment of their recurrent solid tumours by immunon-
cology.
Patients diagnosis: NSCLC: 8 ( 3 × 2nd. Line; 5 × 3rd. Line)
Urothelium: 5 ( 5 × 2nd. Line)
Melanoma 4 ( all metastatic 1st. Line)
H&N 4 ( 1 × 2nd. Line; 3 × 3rd. Line)
PE- Ca Skin 2 ( both 2nd. Line)
M. Hodgkin 1 ( 4th. Line)
Results: We saw a very good benet especially in head and neck tumours:
One patient achived in 3rd. Line a CR more for then 18 months (on
going).
3/4 with head and neck have an on going PR for 12, 14 and 17 months.
2/8 whith NSCLC responded in 3rd. Line for more then 30 months at an
age of 81 and 88 years.
One patient with SCC o he skin is on going with a VGPR for 35 months
at the age of 89 years.
In totally we saw : 1/24 CR, 3/24 VGPR, 10/24 PR, 5/24 SD, 5/24 PD.
Side eects were rare. One male patient developed a diabetes and was
treatet in a hospitaly successfully.
Immunoncology therapie was given always in out patients setting.
Conclusion: Immunoncology therapy is well proven in many tumour
entities and may become a leading role in rst line treatment scedules.
ere could be a chance of long time surviving for some patients.
Further studies are needed.
Gynecological Cancer
Poster
891
Counseling for Hereditary Breast and Ovarian Cancer at
Charité - Characteristics of the Counselees
Malina Helms1; Nanette Kalmbach1; Carolin Neeb1; Julia Kussmaul1;
Dorothee Speiser1
1Charité Universitätsmedizin Berlin, Zentrum für Familiären Brust- und
Eierstockkrebs, Deutschland
Purpose: About 5-10% of all breast cancers and 15-20% of all ovarian
cancers are due to pathogenic mutations in dierent risk genes. As one of
20 centers in Germany, the Center of Hereditary Breast and Ovarian Can-
cer at Charité oers genetic counseling. Extensive data of the collective
was now evaluated for the rst time. e aim of this study was to ease the
preparation for counseling and gather information for more individual-
ized counseling.
Methods: Data from 2531 counselees at the Charité -Centre of 2016 and
2017 were retrospectively evaluated. Special emphasis was laid on socio-
demographic data, results of genetic testing and mutation frequencies.
Results: 2531 counselees were almost exclusively female (n = 2493;
98.5%), 42.9 years old on average and came to the center for the rst time
(n = 2198; 86.8%). 2287 (90.4%) counselees met the inclusion criteria. Of
these, 863 (37.7%) were already diagnosed with breast or ovarian cancer.
1367 (59.8%) were genetically tested. Mutations were detected in 545
(39.9%) tested persons. Most mutations were detected in BRCA1, BRCA2,
CHEK2 and ATM. e highest mutation frequency was found among per-
sons from families with both breast and ovarian cancer and in patients
with TNBC. A signicant correlation was found between mutation fre-
quency in TNBC and age at rst diagnosis.
Conclusions: In summary, these results provide a comprehensive over-
view of the care structure at the Charité -Center, enabling more individu-
alized counseling and more focused preparation for the consultation.
References:
1. Speiser D. Beratung von Ratsuchenden mit familiärer Brust- oder Eierstock-
krebsbelastung. Gynakol Geburtsmed Gynakol Endokrinol. 2017;13(2):170-86.
2. Waha A. et al. Konsensusempfehlung des Deutschen Konsortiums Familiärer
Brust- und Eierstockkrebs zum Umgang mit Ergebnissen der Multigenanalyse.
Geburtsh Frauenheilk 2017; 77. 2018;39:187-93.
Disclosure Statement: No information provided.
893
Inltration of MDR1 Positive M2 Macrophages Leads to Worse
Prognosis in Ovarian Cancer
Susann Badmann1; Sabine Heublein1,2; Doris Mayr3; Yue Liao1;
Thomas Kolben1; Susanne Beyer1; Anna Hester1; Christine Zeder-Göss1;
Alexander Burges1; Sven Mahner1; Udo Jeschke1,4; Fabian Trillsch1;
Bastian Czogalla1
1Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der
Universität München, München, Deutschland
2Frauenheilkunde und Geburtshilfe, Universitätsklinikum Heidelberg,
Heidelberg, Deutschland
3Pathologisches Institut, Ludwig-Maximilians-Universität München, München,
Deutschland
4Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Augsburg,
Augsburg, Deutschland
Purpose: MDR1 expression on tumor cells has been widely investigated
in context of drug resistance. However, the role of MDR1 on the immune
cell inltrate of solid tumors is widely unknown. Aim of this study is
to clarify the prognostic signicance of a MDR1 positive immune cell
inltrate in epithelial ovarian cancer (EOC) and to identify the MDR1
positive leucocyte subpopulation.
Methods: MDR1 expression has been analyzed by immunohistochem-
istry in 156 EOC samples. In addition to MDR1 positive cancer cells,
we detected a MDR1 positive leucocyte inltrate, which was quantied,
grouped by low inltrate and high inltrate, correlated with clinical and
pathological data and compared in terms of OS. To identify the immune
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cell subpopulation immunouorescence co-staining for MDR1 and dier-
ent immune cell markers was performed.
Results: A high number of immune cells inltrating EOC samples of
all subtypes was detected. Signicant correlations of the leucocyte inl-
trate with Her2 (cc=0.258, p=0.005) and TA-MUC1 (cc=0.202, p=0.022)
expression of the tumor were found. A MDR1 positive leucocyte inl-
trate leads to decreased OS (median OS 69.1 vs. 94.3 months, p=0.057)
with long term eects that turn signicant from 24 month up to 9 years
(median OS 97.4 vs. 128.7 months, p=0.031). Especially in TA-MUC1
positive patients (median OS 53.8 vs. 92.6 months, p=0.021) the OS was
signicantly lower with a high MDR1 positive immune cell inltrate.
e subpopulation of M2 macrophages was identied by immunouo-
rescence co-staining, expressing MDR1, the M2 marker CD163, and the
pan-macrophage marker CD68.
Conclusions: Inltration with MDR1 positive M2 macrophages leads to
poor prognosis in long term survival of EOC patients, especially in the
TA-MUC1 positive subgroup. Further understanding of the interaction of
M2 macrophages, MDR1 and TA-MUC1 is a key point to overcome drug
resistance in ovarian cancer.
913
A Comparison of Laparoscopic vs Open Procedure in
Patients with Pelvic and Paraaortic Lymph Node Dissection
for Intermediate and High-Risk Endometrial Cancer – A
Retrospective Cohort Study on Overall and Recurrence Free
Survival
Thomas Papathemelis1; Helen Oppermann2; Stella Gra3;
Michael Gerken2; Sophia Scharl4; Anton Johann Scharl1;
Elisabeth C. Inwald5; Atanas Ignatov5; Olaf Ortmann5; Armin Pauer2;
Michael Patrick Lux6; Monika Klinkhammer-Schalke2
1Klinikum St. Marien, Frauenklinik, Amberg, Deutschland
2Tumor center - Institute for quality assurance and health services research,
University of Regensburg, Regensburg, Deutschland
3Universitätsklinikum Erlangen, Frauenklinik, Friedrich-Alexander-Universität
Erlangen, Erlangen, Deutschland
4Department of Radiation Oncology, Klinikum rechts der Isar, Technische
Universität München , München, Deutschland
5Department of Gynecology and Obstetrics, University Medical Center
Regensburg, Regensburg, Deutschland
6Klinik für Gynäkologie und Geburtshilfe, St. Vincenz-Krankenhaus Paderborn,
Paderborn, Deutschland
Purpose: e primary therapy for intermediate and high risk endometri-
al cancer includes pelvic and paraaortic lymph node evaluation. Laparo-
scopic surgery is an increasingly popular intervention due to decreased
risk and better short term morbidity; however, a recent study casts doubt
on the benet of this approach in terms of oncological safety. In this can-
cer registry study, we sought to evaluate the benet of laparoscopy and
retrospectively compared overall survival, recurrence rates, and recur-
rence-free survival among patients with intermediate and high-risk endo-
metrial cancer who underwent either laparoscopic or open surgery.
Methods: e study included 419 patients who are recorded in clinical
cancer registries in Regensburg and Erlangen/Nuremberg from 2011 to
2017. We employed Kaplan-Meier-method, and univariable and mul-
tivariable Cox-regression in order to compare overall survival, recur-
rence rates, and recurrence free survival in 110 patients, who underwent
laparoscopic, with 309 patients, who underwent open surgery. To address
confounding bias, we also performed a propensity score matching (PSM)
analysis including 357 patients (laparoscopy: n = 107; open surgery:
n = 250).
Results: We found a benet for laparoscopic over open surgery in patients
with intermediate and high-risk endometrial cancer for overall survival in
both univariable (p = 0.002; PSM: p = 0.016) and multivariable analysis
(p = 0.019; PSM: p = 0.007). In contrast, there was no statistically sig-
nicant dierence between both patient groups regarding the cumulative
recurrence rates. A univariable analysis identied a signicant benet for
laparoscopy regarding recurrence free survival (p = 0.003; PSM: p = 0.029)
but a multivariable analysis failed to conrm this nding (p = 0.108; PSM:
p = 0.118).
Conclusions: Our study provides evidence that with regard to oncological
safety laparoscopic systematic lymphadenectomy does not fare worse than
open surgery in the treatment of endometrial cancer.
Disclosure Statement: e authors declare no conict of interest.
1028
Familial Breast and Ovarian Cancer and the Role of Resident
Gynecologists
Stephanie Häring1; Karen Fechner2; Christine Olbrich2; Markus A. Feufel3;
Dorothee Speiser2; Friederike Kendel1
1Institut für Geschlechterforschung in der Medizin, Charité-Universitätsmedizin
Berlin
2Klinik für Gynäkologie mit Brustzentrum, Charité-Universitätsmedizin Berlin
3Institut für Psychologie und Arbeitswissenschaft (IPA), Fachgebiet
Arbeitswissenschaft, Technische Universität Berlin
Purpose: 5-10% of all mamma carcinomas and 10-15% of all ovarian car-
cinomas result from genetic mutations1. As resident gynecologists (RGs)
know their patients’ family history, they can help to signicantly improve
early detection of patients at risk for familial breast/ovarian cancer and
inform them about possible next steps such as specialized genetic counsel-
ing. e aim of this study was to examine how BRCA patients experience
the interaction with their RG regarding the topic of genetic counseling
and testing.
Methods: We conducted a semi-structured focus group interview with
BRCA mutation carriers (n = 9) and assessed the material according to
source and timing of referral to genetic counseling as well as womens as-
sociated impressions.
Results: RGs played a minor role in BRCA patients’ course of genetic
counseling and testing: None of the participants had been referred to ge-
netic counseling by her RG. Only one woman was tested before, all other
women aer the onset of a cancer, oen in spite of a family history of
gynecological cancer. Several women expressed that they felt “deprived of
treatment options” since they had not been referred to genetic counseling
earlier.
Conclusions: e experiences of nine women with BRCA indicate that
the topic of genetic counseling and testing is hardly covered in the RG-pa-
tient interaction. is leaves unexploited potential for the early detec-
tion of patients at risk for familial breast/ovarian cancer. If RGs identi-
fy patients at risk at an early stage and refer them to specialized genetic
counseling centers, they can help to improve the care of women at risk
for familial breast/ovarian cancer. Moreover, they foster patient empow-
erment by oering them an enlarged scope of action and better informed
decision-making. To help facilitate the early detection of these women at
risk, we currently design a specialized training to convey the necessary
skills and knowledge to RGs.
Reference:
1. Speiser, D. (2017). Beratung von Ratsuchenden mit familiärer Brust- oder
Eierstockkrebsbelastung. Gynakol Geburtsmed Gynakol Endokrinol, 13(2),
170–186.
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2018
Index
2018
1029
Cytokeratin 7 Expression as Prognostic Marker in Squamous
Cell Carcinoma of the Vulva
Sevinj Wittershagen1; Thore Thiesler2; Thomas Hecking1;
Eva Katharina Egger1; Dominique Könsgen-Mustea1; Alexander Mustea1;
Mignon-Denise Keyver-Paik1; Glen Kristiansen2
1Universitätsklinikum Bonn, Klinik für Gynäkologie und Gynäkologische
Onkologie, Bonn, Deutschland
2Insitut für Pathologie, Universitätsklinilum Bonn, Bonn, Deutschland
Purpose: Patients with squamous cell carcinoma of the vulva (SCCV)
have dierent survival rates even within a tumor stage and nodal status. In
other tumor entities, Cytokeratin 7 (CK7) was identied as a prognostic
marker. e purpose of the study was to investigate the prognostic value
of CK7 expression in patients with SCCV.
Methods: 110 Patients treated between 2002-2017 at the University hos-
pital in Bonn were enrolled in the trial aer ethical agreement Tissue mi-
croarray (TMA) of 110 Specimen of SCCV of patients staged FIGO I-IV
were evaluated with CK7 monoclonal antibodies using Four-Score tech-
nique, based on the intensity of cell staining.Kaplan-Meier, Chi-square
and Log-rank analysis were performed to characterize the prognostic im-
pact of CK7 expression in SCCV patients.
Results: CK7 expression was present in 7 out of 110 specimen only (6.3%).
Median Progression Free Survival was 24 months, 1 out of 36 recurrenc-
es was CK7 positive. Median Overall Survival (OS) in patients with CK7
expression was 47 months (95% CI 20-73 months) in comparison with 97
months (95% CI 84-111 months) in patients with negative CK7 expres-
sion, albeit no signicance could be shown (p=0.174). CK7 expression did
not correlate with tumor stage, grading, nodal status, metastasis, vascular,
or lymphatic invasion.
Conclusion: Median survival was not statistically dierent in patients
with CK7 expression in SCCV although OS diered by 50 months. Fail-
ure to reach signicance was likely caused by the low prevalence of CK7
positive tissue in our study. Expression of CK7 in SCCV therefore remains
a promising prognostic marker and warrants further investigation in a
larger cohort.
1032
Study Protocol of the German Multicentre Study “Evaluation
of a Decision Coaching Program for Structured Decision
Support of Preference Sensitive Decisions within the Context
of Risk-Adapted Prevention for BRCA1/2 (Breast Cancer) Gene
Carriers” (EDCPBRCA)
Frank Vitinius1; Juliane Köberlein-Neu2; Anke Steckelberg3;
Birte Berger-Höger3; Karolina Beifus2; Hannah Fischer1;
Regina Wiedemann4; Anna Isselhard5; Maren Töpper5; Kerstin Rhiem4;
Rita Schmutzler4; Stephanie Stock5
1Department of Psychosomatics and Psychotherapy, Faculty of Medicine,
University Hospital Cologne, University of Cologne, Cologne, Germany
2Center for Health Economics and Health Services Research, Schumpeter School
of Business and Economics , University of Wuppertal, Wuppertal, Germany
3Institute for Health and Nursing Science, Faculty of Medicine, Martin Luther
University Halle-Wittenberg, Halle (Saale)
4Centre for Familial Breast and Ovarian Cancer, University Hospital Cologne
5Institute of Health Economics and Clinical Epidemiology, University Hospital of
Cologne
Background: Female BRCA mutation carriers have an increased lifetime
risk for breast and ovarian cancer compared to the general population.
Women who carry this mutation have several options to deal with their
cancer risk, such as risk-reducing surgeries or intensied breast cancer
screening. Previous research has shown that preferences in this scenario
are highly dependent on aected womens personalities and value-
systems. To support these women in the decision-making process, a
structured decision support consisting of a decision coaching combined
with a decision aid might be helpful.
Methods: A randomized controlled trial will be conducted in order to
compare usual care with a structured decision support alongside usual
care. e decision support program entails a nurse-led decision coaching
as well as an evidence-based patient decision aid. Nurses are qualied by
a four day training in informed decision-making and decision coaching.
Six centers for Familial Breast and Ovarian Cancer in Germany will be
included in the study, with a planned sample size of 398 women.
e primary outcome is the congruence between the preferred and the
actual played role in the decision-making process as measured by the
Control Preferences Scale. It is hypothesized that the structured decision
support will enable women to play the preferred role in the decision-
making process. Secondary outcomes include the knowledge and
attitudes about preventive options, decisional conict, depression and
anxiety, coping self-ecacy, impact of event, and self-concept. A process
evaluation will accompany the study.
Discussion: e EDCP-BRCA study is the rst study to implement and evaluate
a decision coaching combined with a decision aid for healthy BRCA mutation
carriers worldwide.
1035
Epigenetic Signature as a Prognostic Marker for High Grade
Cervical Neoplasia
Alfred Hansel1; Martina Schmitz1; Ingo B. Runnebaum2; Matthias Dürst2
1oncgnostics GmbH, Jena, Deutschland
2Klinik und Poliklinik für Frauenheilkunde und Fortpanzungsmedizin,
Universitätsklinikum Jena, Jena, Deutschland
Objectives: Patients with a persisting hrHPV infection, in particular
HPV16, have an increased risk for developing high grade cervical in-
traepithelial neoplasias (CIN). Nevertheless, most hrHPV infections are
cleared by the immune system. Clinically validated molecular biomarkers
indicative for the development of CIN are still lacking. However, there is
growing evidence that DNA hypermethylation of host DNA may indeed
have prognostic potential.
Methods: In a retrospective, longitudinal study cervical scrapes from 119
patients with the nal histopathology diagnosis CIN3, for whom at least
one sample prior to histopathological diagnosis was available, were ana-
lyzed for methylation of CpG islands in the gene regions ASTN1, DLX1,
ITGA4, RXFP3, SOX17 and ZNF671. e methylation status of these
markers, that comprise the cervical cancer diagnostic test GynTect®, was
determined using methylation-specic PCR and was correlated to histo-
pathology, HPV prevalence and cytology ndings.
Results: Detection of at least two of the six markers was obtained before
histopathological diagnosis CIN3 in 62% of the 119 cases. Twenty % of
cases were methylation positive 18 months prior to histopathological
conrmation of CIN3. In a control group comprising 733 patient samples
with Pap I ndings, the GynTect® detection rate was only 3.4%.
Conclusions: e results of this study underscore the prognostic value of
the six methylation markers for severe cervical dysplasia. We are currently
conducting a prospective trial “GynTect-PRO” which aims to conrm the
prognostic value of the GynTect® methylation markers in patients with
CIN2/3 aged ≤ 24 years who are undergoing watchful waiting for up to
2 years.
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2018
Index
2018
Head and Neck Cancer
Vorträge
900
Comprehensive Genomic and Transcriptomic Analysis of
Primary and Recurrent Head and Neck Cancers
Luisa Bresadola1; Anthony Kong1,2; Martin Löwer1; Valesca Bukur1;
Christoph Ritzel3; David Weber1; Özlem Akilli-Öztürk1; Christian Albrecht1;
Karen Chu1; Hisham Mehanna2; Barbara Schrörs1; Fulvia Vascotto1;
Ugur Sahin3
1TRON - Translational Oncology at the University Medical Center of the
Johannes Gutenberg University Mainz, Mainz, Deutschland
2Institute of Head and Neck Studies and Education (InHANSE), Institute of
Cancer and Genomic Sciences, Birmingham, United Kingdom
3University Medical Center of the Johannes Gutenberg University Mainz, Mainz,
Deutschland
Purpose: Head and neck squamous cell carcinomas (HNSCCs) are a
group of heterogeneous diseases arising from the epithelial cells of oral
cavity, pharynx, larynx, nasal cavity and salivary glands. Major risk fac-
tors are smoking, excessive alcohol use and human papillomavirus (HPV)
infection. Despite aggressive treatment, up to 50% of the patients relapse
within three years and have very poor prognoses. In this study, we in-
vestigated how the genetic landscape and the patterns of gene expression
change during tumor evolution, upon recurrence and aer treatment. is
information can improve our understanding of tumor progression and
help in predicting it, also in connection to patient history.
Methods: We sequenced whole exome and transcriptome of matched
primary and recurrent tumor samples from nine patients, with dierent
treatment and patient histories. ese data were used to call somatic Sin-
gle Nucleotide Variants (sSNVs), perform a dierential expression analy-
sis and quantify immune cell inltration in the tumor.
Results: e analysis of sSNVs showed that tumor mutational burden var-
ies considerably across patients, but is generally higher in recurrent sam-
ples than in primary tumors: part of the mutation prole is shared, but in
the majority of the patients recurrent samples acquire additional sSNVs.
A dierential gene expression analysis highlighted ca. 250 genes that are
consistently up- or down-regulated in the recurrent samples compared to
the primary tumor, in spite of the diverse patient histories. Immune cell
inltration in the tumor is overall higher in primary than in recurrent
samples, although heterogeneity across patients is substantial in this re-
gard, too.
Conclusions: Altogether, these results highlight the complexity and the
important dierences occurring in the genomic and transcriptomic land-
scape of HNSCC samples, and support the administration of individual-
ized immunotherapy treatments to patients aected by this cancer entity.
Disclosure Statement: Valesca Bukur and Christian Albrecht: paid consultants/
part-time employees of BioNTech SE.
Ugur Sahin: co-founder and shareholder of TRON, co-founder and CEO of
BioNTech SE.
Anthony Kong: received fees for consulting, advisory, speaker’s roles and/or
research funding from PUMA BioTechnology, AstraZeneca, Merck, MSD, Bris-
tol-Myers Squibb, Avvinity erapeutics.
Hisham Mehanna: personal nancial interests with AstraZeneca, MSD, GSK,
Sano Pasteur, Merck, Warwickshire Head Neck Clinic Ltd; institutional nancial
interests with AstraZeneca, GSK PLC, Sano Pasteur, MSD, GSK Biologicals,
Silence erapeutics; leadership roles: Chief of Liteform Trial Steering Committee,
Chair of NIMRAD Trial Steering Committee, President of the British Association
of Head Neck Oncologists, Trial Steering Group member of the MRC CTU Cancer
Trials Steering Committee, Council member of the International Association of
Oral Oncology, Director of the Institute for Head Neck Studies and Education,
Secretary of the Head Neck Cancer InterGroup.
All other authors have no conict of interest.
1053
Tpextreme Randomized Trial: TPEX Versus Extreme Regimen
in 1st Line Recurrent/Metastatic Head & Neck Squamous Cell
Carcinoma (R/M HNSCC), Updated Analysis
1Keilholz, U.; 2Guigay, J.; 3Fayette, J.; 4Mesia, R.; 5Lafond, C.;
6Saada-Bouzid, E.; 7Georois, G.; 8Martin, L.; 9Cupissol, D.; 10Capitain, O.;
11Castanie, H.; 12Vansteene, D.; 1Schafhausen, P.; 13Dubos Arvis, C.;
14Even, C.; 15Sire, C.; 16Delhommeau, M.; 16Michel, C.; 17Bourhis, J.;
14Auperin, A.
A joint trial of the GORTEC (France), AIO-Studien-gGmbH (Germany),
TTCC (Spain)
In collaboration with GETTEC-GERCOR and with H&N UNICANCER
group (France)
1Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
2Department of Medical Oncology, Antoine Lacassagne Comprehensive Cancer
Centre, FHU OncoAge, Université Côte d’Azur, Nice, France
3Centre Léon Bérard, Medical Oncology, Lyon, France
4Catalan Institute of Oncology, IDIBELL, Barcelona, Spain
5Clinique Victor Hugo, Le Mans, France
6Centre Antoine Lacassagne, Université Côte d’Azur, Nice, France
7Institut de Cancérologie de Lorraine, Vandoeuvre-Lés-Nancy, France
8Clinique des Ormeaux, Le Havre, France
9Institut du Cancer de Montpellier, Montpellier, France
10Institut de Cancérologie de l’Ouest, Site Paul Papin, Angers, France;
11Hôpital Prive du Conuent S.A.S, Nantes, France
12Institut de Cancérologie de l’Ouest–René Gauducheau, Nantes, France;
13Centre François Baclesse, Oncology, Caen, France
14Gustave Roussy, Villejuif, France
15Groupe Hospitalier Bretagne Sud-Radiothérapie-Oncologie, Lorient, France;
16GORTEC, Tours, France
17Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Purpose: Aer promising results from the GORTEC TPEx phase II trial,
the role of taxane instead of 5FU in 1st-line R/M HNSCC chemotherapy
(CT) remained to be conrmed by comparing TPEx to the reference
EXTREME regimen.
Methods: Randomized (1:1), open-label trial. Main inclusion criteria
were R/M HNSCC not suitable for locoregional treatment, age 18-70
years, PS <2, creatinine clearance >60ml/min, prior cisplatin <300 mg/m².
Reference EXTREME regimen (arm A: 6 cycles every 3 weeks (Q3W) of
5FU–cisplatin-cetuximab (cetux) followed by weekly cetux maintenance)
was compared to TPEx regimen (arm B: 4 cycles Q3W of docetaxel 75mg/
m²–cisplatin 75mg/m²- cetux 250mg/m² with mandatory G-CSF support
followed by every 2W cetux 500mg/m² maintenance). e primary end-
point was Overall Survival (OS).
Results: 539 pts were enrolled in 37 mo. Median age was 60 years, 93%
were smokers, 40% had oropharyngeal tumor (p16 or HPV DNA posi-
tive in 28%). In arm A, 44% of pts received all CT cycles vs 72% in arm
B. Delays in administration were more frequent in arm A (27% vs 10%).
Cisplatin was more frequently switched to carboplatin in arm A (34% vs
9%). Toxicity was lower in arm B: 34% pts had grade ≥4 adverse events
during CT in arm B vs 50% in arm A (p<0.001). Less pts in arm A started
maintenance than in arm B (53% vs 73%). At time of analysis, the median
follow-up duration was >30 mo and 406 pts had died. OS was not sig-
nicantly dierent between arms: HR=0.87 (95%CI: 0.71-1.05), p=0.15.
Median OS was 13.4 mo in arm A vs 14.5 in arm B. 2-year OS rate was
21.0% in arm A vs 28.6% in arm B. Median PFS was 6.1 mo in arm A vs
6.0 in arm B.
Conclusions: is large randomized trial conrmed the encouraging sur-
vival results of the TPEx regimen observed in the rst phase II. Despite
lack of signicant OS increase, taxane based TPEx regimen appears to be
a new option in 1st line R/M HNSSCC, with a shorter time on CT and
signicantly lower toxicity than the EXTREME regimen.
Reference:
1. J. Guigay et al, J Clin Oncol 37, 2019 (suppl; abstr 6002)
Funding source: Grant from Merck Serono.
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2018
Poster
929
Prognostic Signicance of CD8-Based Immune Status
Inamed, Immune-Excluded and Immune Desert in Head and
Neck Tumors can be Further Subdivided by Regulatory T Cells
Luitpold Distel1; Alessia Echarti1; Rainer Fietkau1; Markus Hecht1
1Strahlenklinik, Universitätsklinikum Erlangen, Erlangen, Deutschland
Purpose: It has been postulated that there are tumors with very low inl-
tration of inammatory cells, i.e. immune deserts, with immune response
limited to the stroma, i.e. immune excluded and the inamed tumors with
many inammatory cells intraepithelially. We studied the prognostic sig-
nicance of CD8, classied according to immune desert, immune exclu-
sion and inammation, as well as the inuence of regulatory T cells, in
tissue sections of 284 HNSSC patients.
Methods: Cytotoxic T cells (CD8+) and regulatory T cells (FoxP3+) were
determined separately in the stromal and intraepithelial compartment by
double staining in 284 tissue samples using image analysis soware.
Results: e division of the tissues into desert (<34 cells per mm2; FoxP3
17.3 stromal, 0.0 intraepithelial), excluded (<334 cells intraepithelial;
190.6 / 46.3) and inamed (>334 cells intraepithelial; 382.3 / 132.4). In
overall survival (Kaplan Meier) the desert group had a median survival of
41 months, excluded 57 m and inamed the best survival with 81 m. In
addition, the importance of FoxP3+ cells in the three groups was analyzed.
In the desert group, stromal FoxP3 had no signicance. In the excluded
group low intraepithelial FoxP3 with 76 m v. 37 m was associated with
clearly better survival. In contrast, high stromal FoxP3 was favorable (94
m v. 44 m) for survival. In Inamed high FoxP3 were favorable, stromal
with >96 m v. 77 m and intraepithelial with >96 m v. 72 m.
Conclusions: In the desert and excluded group, the few cytotoxic cells
(low CD8) were immunosuppressed by high regulatory T cells, leading
to an unfavorable prognosis. In the inamed group, the importance of
regulatory T cells is reversed and a high number leads to a more favorable
prognosis. is could be interpreted as the suppression of inammation
and thus the reduction of inammatory mediators and tumor growth-pro-
moting properties. Although the three groups already dier signicantly
in their prognosis, their importance can be further dierentiated by the
regulatory T cells.
Disclosure: e authors declare no conict of interest.
Immunotherapy Side Eects
Poster
889
Serio - Side Eect Registry in Immuno-Oncology
Rafaela Koutzamanidis1; Dirk Mentzer2; Samuel Knauss3;
Paul J. Bröckelmann4; Jessica Cecile Hassel5; Selma Ugurel-Becker6;
Marianne Pavel7; Florian Nickel8; Melanie Landendinger9; Florian Fuchs7;
Norbert Meidenbauer10; André Jefremow7; Bernhard Manger11;
Ralf Gutzmer12; Carmen Loquai13; Katharina Kähler14; Lisa Zimmer6;
Carola Berking1; Brigitte Keller-Stanislawski2; Lucie Heinzerling Mph1;
Michael Erdmann1; Michael C. Kirchberger1; Frederic Toussaint1
1University Hospital Erlangen, Friedrich-Alexander-University Erlangen-
Nürnberg (FAU), Department of Dermatology, Erlangen, Deutschland
2Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines,
Department Safety of Medicinal Products and Medical Devices, Langen,
Deutschland
3Universitätsmedizin Berlin, corporate member of Freie Universität Berlin,
Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und
Hochschulambulanz für Neurologie, Berlin, Deutschland
4Faculty of Medicine and University Hospital of Cologne, University of Cologne,
Department I of Internal Medicine, Centre of Integrated Oncology Aachen Bonn
Cologne Duesseldorf (CIO ABCD), German Hodgkin Study Group (GHSG), Köln,
Deutschland
5University Hospital Heidelberg, Skin Cancer Center, Department of
Dermatology and National Center for Tumor Diseases (NCT), Heidelberg,
Deutschland
6University Hospital Essen, Department of Dermatology, Venerology und
Allergology, Essen, Deutschland
7Friedrich-Alexander University Erlangen-Nuremberg, University Hospital of
Erlangen, Department of Internal Medicine-1, Erlangen, Deutschland
8University Hospital Erlangen, Department of Neurology, Erlangen, Deutschland
9University Hospital Erlangen, Department of Cardiology, Erlangen,
Deutschland
10University Hospital Erlangen, Department of Internal Medicine 5, Hematology
and Oncology, Erlangen, Deutschland
11University Hospital Erlangen, Department of Medicine 3 - Rheumatology and
Immunology, Erlangen, Deutschland
12Hannover Medical School, Skin Cancer Center Hannover, Department of
Dermatology and Allergy, Hannover, Deutschland
13University Hospital of Mainz, Department of Dermatology, Mainz, Deutschland
14University Hospital of Kiel, Department of Dermatology, Kiel, Deutschland
Purpose: In an era where immunotherapies have become standard for
oncological therapy of a variety of tumor entities, adequate management
of side eects is essential. However, little is known about rare, severe or
complex immune-related adverse events (irAE). us, these cases have to
be analyzed together to gain further understanding of risk factors, occur-
rence, optimal treatment and outcome of these side eects.
Methods: SERIO is an international side eect registry for rare, severe
and/or treatment-refractory side eects induced by immune checkpoint
blockade, i.e. CTLA4- and PD1/PD-L1 inhibitors or other immunother-
apies. e patients´ medical history, symptoms, diagnostic ndings and
management of the side eects as well as the outcome are documented.
Results: Until now, more than 1,000 cases of rare, severe, complex or
treatment-refractory side eects induced by nivolumab, pembrolizumab,
atezolizumab, cemiplimab or ipilimumab have been assessed. From these
analyses, recommendations, pathogenetic studies and several publications
have been developed from it, also in special patient cohorts. In coopera-
tion with the Paul-Ehrlich-Institute the registry is currently being devel-
oped for online use.
Conclusions: e SERIO registry will increase knowledge on rare and
severe side eects induced by immunotherapy. Shared experiences will
enable better management of side eects and better patient information
with regard to outcome of side eects thus reducing patient morbidity and
mortality. Eventually, it will enable to better understand pathogenesis and
prediction of irAEs.
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2018
Index
2018
Lung Cancer
Vorträge
875
Updated Results from the Phase 3 ALTA1L Trial of Brigatinib
(BRG) vs. Crizotinib (CRZ) in ALK Inhibitor-Naive Advanced
ALK + NSCLC
Frank Griesinger1; D. Ross Camidge2; Hye Ryun Kim3; Myung-Ju Ahn4;
James Chih-Hsin Yang5; Ji Youn Han6; Maximilian Hochmair7;
Ki Hyeong Lee8; Angelo Delmonte9; Maria Rosario Garcia Campelo10;
Dong-Wan Kim11; Enriqueta Felip12; Raaele Califano13; Alexander Spira14;
Scott N Gettinger15; Marcello Tiseo16; Huamao M Lin17; Quanhong Ni17;
Pingkuan Zhang17; Sanjay Popat18
1Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Deutschland
2University of Colorado Cancer Center, Aurora, United States
3Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Südkorea
4Samsung Medical Center, Seoul, Südkorea
5National Taiwan University Hospital, Taipei, Taiwan
6National Cancer Center, Goyang, Südkorea
7Department of Respiratory and Critical Care Medicine, Krankenhaus Nord –
Klinik Floridsdorf, Vienna, Österreich
8Chungbuk National University Hospital, Cheongju, Südkorea
9Scientic Institute of Romagna for the Study and Treatment of Cancer, Meldola,
Italien
10Complejo Hospitalario Universitario A Coruna Hospital Teresa Herrera-Materno
Infantil, Coruna, Spanien
11Seoul National University Hospital, Seoul, Südkorea
12Vall d’Hebron University Hospital, Barcelona, Spanien
13The Christie NHS Foundation Trust, Manchester, United Kingdom
14Virginia Cancer Specialists and US Oncology Research, The Woodlands, United
States
15Yale Cancer Center, New Haven, United States
16University Hospital of Parma, Parma, Italien
17Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda
Pharmaceutical Company Limited, Cambridge, United States
18Royal Marsden Hospital, London, United Kingdom
Purpose: We report results of the ALTA-1L trial (NCT02737501) from the
second interim analysis, planned at 75% of 198 expected events.
Methods: Patients (pts) with ALK inhibitor–naive advanced ALK+ NS-
CLC and ECOG PS 0–2 were enrolled and stratied by baseline (BL)
brain metastases and prior chemotherapy. One prior chemotherapy for
advanced NSCLC and asymptomatic CNS metastases were allowed. All
pts had brain MRI at each tumor assessment. Pts were randomized 1:1
to BRG 180 mg QD (with 7-day lead-in at 90 mg) or CRZ 250 mg BID.
Pts in the CRZ arm were oered BRG at progression. Primary endpoint:
BIRC-assessed PFS (RECIST v1.1). Secondary endpoints included con-
rmed ORR, conrmed iORR, iPFS by BIRC, OS, and safety.
Results: 275 pts were randomized (BRG/CRZ, n=137/138); median age
58/60 y. 26%/27% received prior chemotherapy; 29%/30% had BL brain
metastases. As of 28 Jun 2019, median follow-up was BRG/CRZ: 24.9/15.2
mo, with 150 (63/87) PFS events. HR of BIRC-assessed PFS was 0.49 (95%
CI 0.35–0.68, log-rank P<0.0001); BRG mPFS (95% CI) was 24.0 mo
(18.5–NR) vs CRZ 11.0 mo (9.2–12.9). Investigator-assessed PFS HR was
0.43 (0.31–0.61, log-rank P<0.0001); median 29.4 vs 9.2 mo. Conrmed
ORR for BRG was 74% (66–81) vs CRZ 62% (53–70); median DoR was
NR (19–NR) vs CRZ 14 mo (9–21). OS was immature (total events: 33/37,
BRG/CRZ). In pts with BL brain metastases, BIRC-assessed PFS HR
(BRG/CRZ, n=40/41, per investigator) was 0.25 (0.14–0.46) and iPFS HR
(n=47/49, by BIRC) was 0.31 (0.17–0.56); log-rank P<0.0001 for both. In
pts without BL brain metastases (n=97/97), PFS HR was 0.65 (0.44–0.97,
log-rank P<0.0298). In pts with measurable iCNS disease (BRG/CRZ,
n=18/23), conrmed iORR was BRG 78% (52–94) vs CRZ 26% (10–48);
P=0.0014; median iDoR NR (6–NR) vs 9 mo (4–9). Most common TEAEs
grade ≥3: BRG: increased CPK (24.3%) and lipase (14.0%), hypertension
(11.8%); CRZ: increased ALT (10.2%), AST (6.6%), and lipase (6.6%). Any
grade ILD/pneumonitis (BRG/CRZ): 5.1%/2.2%; discontinuations due to
AE: 12.5%/8.8%.
Conclusions: BRG showed durable PFS superiority vs CRZ in ALK inhib-
itor–naive ALK+ NSCLC.
Study funder: ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda
Pharmaceutical Company Limited
884
Impower110: Interim OS Analysis of a Phase III Study Of
Atezolizumab (ATEZO) vs Platinum-Based Chemotherapy
(Chemo) as 1L Treatment (TX) in PDL1–Selected NSCLC
Niels Reinmuth1; David Spigel2; Filippo De Marinis3; Giuseppe Giaccone4;
Alain Vergnenegre5; Carlos Henrique Barrios6; Masahiro Morise7;
Enriqueta Felip8; Zoran Andric9; Sarayut Geater10; Mustafa Özgüroglu11;
Simonetta Mocci12; Mark Mccleland12; Ida Enquist12; Kim Komatsubara12;
Yu Deng12; Hiroshi Kuriki12; Xiaohui Wen12; Jacek Jassem13; Roy S. Herbst14
1Asklepios Lung Clinic München-Gauting, Gauting, Deutschland
2Sarah Cannon Research Institute, Nashville, United States
3European Institute of Oncology, Milan, Italien
4Lombardi Comprehensive Cancer Center, Washington DC, United States
5Thoracic Oncologic Unit, Limoges University Hospital, Limoges, Frankreich
6PUCRS School of Medicine, Porto Alegre, Brasilien
7Nagoya University Graduate School of Medicine, Aichi, Japan
8Vall d’Hebron University Hospital, Barcelona, Spanien
9Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia
10Prince of Songkla University , Songkhla, Thailand
11Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul,
Turkey
12Genentech Inc., South San Francisco, United States
13Medical University of Gdansk, Gdansk, Poland
14Yale School of Medicine, New Haven, United States
Background: PD-L1/PD-1–inhibitors (CPI) as monotherapy (mono) or
combined with doublet chemo (± bevacizumab) are 1L tx options in met-
astatic NSCLC, with choice of agent(s) determined by PD-L1 expression.
For patients (pts) ineligible for combination therapy, CPI mono remains
an attractive tx choice. IMpower110 evaluated atezo as 1L tx in PD-L1–
selected pts.
Methods: IMpower110 (NCT02409342) enrolled 572 chemo-naive pts
with stage IV nonsquamous [nsq] or squamous [sq] NSCLC, PD-L1 ex-
pression ≥ 1% on tumour- (TC) or tumour-inltrating immune cells (IC),
measurable disease by RECIST 1.1 and ECOG PS 0-1. PD-L1 expression
was centrally evaluated (VENTANA SP142 IHC assay) and classied as
TC/IC3 (TC ≥ 50% or IC ≥ 10% PD-L1+), as TC/IC2-3 (TC ≥ 5% or IC ≥
5% PD-L1+) or TC/IC1-3 (TC ≥ 1% or IC ≥ 1% PD-L1+). Pts were ran-
domized 1:1 to receive atezo 1200 mg IV q3w (Arm A) or platinum-based
chemo (Arm B; 4 or 6 21-day cycles). Arm B nsq pts received cisplatin
(cis) 75 mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed 500 mg/m2
IV q3w; Arm B sq pts received cis 75 mg/m2 + gemcitabine (gem) 1250
mg/m2 or carbo AUC 5 + gem 1000 mg/m2 IV q3w. e primary endpoint
of OS is tested hierarchically in wild-type (WT; EGFR/ALK negative) pts
(TC/IC3 then TC/IC2-3 then TC/IC1-3).
Results: e 3 primary ecacy populations included 554 TC1-3 or IC1-
3-WT pts, 328 TC2-3 or IC2-3-WT pts, and 205 TC3 or IC3-WT pts.
Within the TC3 or IC3-WT population, atezo improved median OS by 7.1
mo (HR 0.595; P = 0.0106) vs chemo (median follow-up 15.7 mo). Median
OS-gain in the TC2-3 or IC2-3-WT group aer atezo was 3.3. mo (HR
0.717; P = 0.0416) but not signicant in the entire population. e safety
population comprised 549 pts. Treatment-related/grade 3-4 AEs occurred
in 60.5%/12.9% (Arm A) or 85.2%/44.1% (Arm B), respectively.
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Conclusions: At this interim analysis, IMpower110 met the primary OS
endpoint with statistically signicant and clinically meaningful improve-
ment in the TC3 or IC3-WT population. e safety prole favored Arm A
with no new or unexpected safety signals seen.
Presented at ESMO 2019, LBA 78, Spigel et al. Reused with permission
886
Impower133: Updated Overall Survival (OS) Analysis of First-
Line (1L) Atezolizumab (ATEZO) + Carboplatin + Etoposide in
Extensive-Stage SCLC (ESSCLC)
Martin Reck1; Stephen V. Liu2; Aaron S. Manseld3; Tony Mok4;
Arnaud Scherpereel5; Niels Reinmuth6; Marina C. Garassino7;
Javier De Castro Carpeno8; Raaele Califano9; Makoto Nishio10;
Francisco Orlandi11; Jorge Arturo Alatorre Alexander12; Ticiana Leal13;
Ying Cheng14; Jong-Seok Lee15; Sivuonthanh Lam16; Mark Mccleland16;
Yu Deng16; See Phan16; Leora Horn17
1Lung Clinic Grosshansdorf, Grosshansdorf, Deutschland
2Lombardi Comprehensive Cancer Center, Georgetown University, Washington
DC, United States
3Division of Medical Oncology, Mayo Clinic, Rochester, United States
4State Key Laboratory of South China, The Chinese University of Hong Kong,
Hong Kong, Hong Kong
5CHU Lille, University of Lille, Lille, Frankreich
6Thoracic Oncology, Asklepios Clinics Munich-Gauting, Gauting, Deutschland
7Thoracic Oncology Unit, Instituto Nazionale dei Tumori, Milan, Italien
8Hospital Universitario La Paz, Madrid, Spanien
9Department of Medical Oncology, Christie NHS Foundation Trust, Manchester,
United Kingdom
10The Cancer Institute Hospital, , Tokyo, Japan 11Instituto Nacional del Tórax,
Prosalud , Tokyo, Japan
11Prosalud Oncología, Instituto Nacional del Tórax, Santiago, Chile
12Health Pharma Professional Research, Mexico City, Mexico
13Carbone Cancer Center, University of Wisconsin , Madison, United States
14Jilin Cancer Hospital, Jilin, China
15Seoul National University Bundang Hospital, Seoul National University College
of Medicine, Seongnam,
16Genentech Inc., South San Francisco, United States
17Vanderbilt University Medical Center, Nashville, United States
Background: IMpower133 (NCT02763579), a global Phase I/III, dou-
ble-blind, randomized, placebo-controlled trial, showed that adding atezo
(anti–PD-L1) to 1L carboplatin + etoposide for ES-SCLC led to a statis-
tically and clinically signicant improvement in OS and progression-free
survival (PFS) vs carboplatin + etoposide alone. is combination was US
FDA–approved in March 2019. Here we present an exploratory updated
OS analysis of IMpower133.
Methods: Patients (pts) without prior systemic tx for ES-SCLC were en-
rolled. PD-L1 testing was not required for enrolment eligibility, but tis-
sue was collected when possible. Pts were randomised 1:1 to receive four
21-day cycles of carboplatin (AUC 5 mg•mL/min IV, Day 1) + etoposide
(100 mg/m2 IV, Days 1-3) with either atezo (1200 mg IV, Day 1) or place-
bo (PBO), then maintenance therapy with atezo or PBO until intolerable
toxicity or progression. Pts meeting predened criteria could receive tx
beyond progression. Coprimary endpoints were OS and investigator-as-
sessed PFS. OS interim and nal analyses were planned for ≈ 240 and ≈
306 OS events, respectively. Since OS was statistically signicant at the
interim analysis, an exploratory updated OS analysis was conducted, and
exploratory biomarker analyses are in progress.
Results: 201 pts were randomized to the atezo group and 202 to the PBO
group. At this updated analysis, 302 OS events had been observed. Median
follow-up was 22.9 mo. Median OS remained 12.3 mo in the atezo group
and 10.3 mo in the PBO group (HR, 0.76 [95% CI: 0.60, 0.95]; descriptive
P = 0.0154). Cumulative survival rates at 6, 12 and 18 mo were 86%, 52%
and 34% in the atezo group, and 83%, 39% and 21% in the PBO group,
respectively. Other ecacy analyses, including by PD-L1 status, will be
presented.
Conclusion: e addition of atezo to carboplatin and etoposide contin-
ued to provide improvement in OS for 1L ES-SCLC. ese results further
support this regimen as the new standard of care for untreated ES-SCLC.
Presented at ESMO 2019, FPN 1736O, Reck et al. Reused with permission
1008
Nivolumab (N) + Low-Dose Ipilimumab (I) vs Platinum-Doublet
Chemotherapy (Chemo) as First-Line (1L) Treatment (tx) for
Advanced Non-Small Cell Lung Cancer (NSCLC): Checkmate
227 Part 1 Final Analysis
Martin Reck1; Solange Peters2; Suresh Ramalingam3; Luis Paz-Ares4;
Reyes Bernabe Caro5; Bogdan Zurawski6; Sang-We Kim7;
Aurelia Alexandru8; Lorena Lupinacci9; Emmanuel de la Mora Jimenez10;
Hiroshi Sakai11; István Albert12; Alain Vergnenegre13; Hossein Borghaei14;
Julie R. Brahmer15; Kenneth O’byrne16; William J. Geese17;
Prabhu Bhagavatheeswaran17; Faith E. Nathan18; Matthew D. Hellmann19
1Airway Research Center North, German Center for Lung Research, LungenClinic
Grosshansdorf, Grosshansdorf, Deutschland
2Oncology Department, Centre hospitalier universitaire Vaudois (CHUV),
Lausanne University, Lausanne, Schweiz
3Department of Hematology and Medical Oncology, Winship Cancer Institute,
Emory University, Atlanta, United States
4Medical Oncology Department, Hospital Universitario Doce de Octubre, CNIO,
Universidad Complutense & CiberOnc, Madrid, Spanien
5Medical Oncology Department, Hospital Universitario Virgen Del Rocio, Seville,
Spanien
6Chemotherapy Department, Ambulatorium Chemioterapii, Bydgoszcz, Poland
7Medical Oncology Department, Asan Medical Center, Seoul, Südkorea
8Medical Oncology Department, Institute of Oncology „Prof.Dr.Alexandru
Trestioreanu“ Bucha, Bucharest, Romania
9Clinical Oncology Department, Hospital Italiano De Buenos Aires, Buenos Aires,
Argentinien
10Medical Oncology Department, Instituto Jalisciense De Cancerología,
Guadalajara, Jalisco, Mexico
11Thoracic Oncology Department, Saitama Cancer Center, Saitama, Japan
12Pulmonary Department, Matrai Gyogyintezet, Matrahaza, Ungarn
13Medical Oncology Department, Limoges University Hospital, Limoges,
Frankreich
14Hematology and Oncology Department, Fox Chase Cancer Center,
Philadelphia, United States
15Oncology Department, Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins, Baltimore, United States
16Medical Oncology, Princess Alexandra Hospital, Brisbane, Australien
17Global Biometric Sciences, Bristol-Myers Squibb, Princeton, United States
18Oncology Clinical Development, Bristol-Myers Squibb, Princeton, United
States
19Memorial Sloan-Kettering Cancer Center, New York, United States
Purpose: Part 1 of CheckMate 227 (NCT02477826), a phase 3 study in
1L NSCLC, previously met one of its dual primary endpoints, progres-
sion-free survival (PFS) with N+I vs chemo in patients (pts) with tumor
mutational burden ≥ 10 mut/Mb. We report the primary endpoint of over-
all survival (OS) for N+I vs chemo in pts with tumor PD-L1 ≥ 1%.
Methods: Pts were chemo-naive, with stage IV or recurrent NSCLC with-
out EGFR or known ALK alterations, ECOG PS 0–1. Pts with PD-L1 ≥ 1%
were randomized 1:1:1 to N 3 mg/kg Q2W + I 1 mg/kg Q6W (n = 396),
N 240 mg Q2W (n = 396), or histology-based chemo (n = 397); pts with
PD-L1 < 1% were randomized 1:1:1 to N 3 mg/kg Q2W + I 1 mg/kg Q6W
(n = 187), N 360 mg Q3W + chemo (n = 177), or chemo (n = 186). Pts
were stratied by histology and treated until progression, unacceptable
toxicity, or for 2 y of immunotherapy.
Results: Baseline characteristics were balanced across tx arms. Minimum
follow-up for OS was 29.3 mo. For pts with PD-L1 ≥ 1%, median OS (95%
CI) was 17.1 mo (15.0–20.1) with N+I vs 14.9 mo (12.7–16.7) with chemo
(HR 0.79, 97.72% CI 0.65–0.96; P = 0.007). HR for PFS was 0.82 (95% CI
0.69–0.97), objective response rate was 35.9% (N+I) vs 30.0% (chemo),
and median duration of response was 23.2 mo vs 6.2 mo. In pts with PD-
L1 < 1%, median OS was 17.2 mo with N+I and 12.2 mo with chemo
(HR 0.62, 95% CI 0.48–0.78) and in all randomized pts, 17.1 mo and 13.9
mo (HR 0.73, 95% CI 0.64–0.84). N+I showed enhanced ecacy vs N
in PD-L1 ≥ 1% and vs N+chemo in PD-L1 < 1%. Grade 3–4 tx-related
adverse event rates in all randomized pts were 33% (N+I), 19% (N), and
36% (chemo).
Conclusions: CheckMate 227 met its primary endpoint of signicantly
improved OS with N+I vs chemo in 1L advanced NSCLC with PD-L1 ≥
1%. OS was also improved with N+I in PD-L1 < 1% and in all randomized
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pts. Safety was consistent with prior reports in NSCLC. N+I may represent
a new chemo-free tx option for 1L advanced NSCLC.
Disclosure Statement:
Funding: BMS
Previously presented at ESMO 2019, FPN LBA4_PR, Peters et al. Reused
from: Ann Oncol 2019; 30 (Suppl_5): v193-v194, doi:10.1093/annonc/
mdz394.075, by permission of Oxford University Press on behalf of ESMO.
Poster
894
Stage IV Lung Cancer - Cost-Eectiveness of the Real-World
Administration of Chemotherapy and Add-on Viscum Album
L. Compared to Chemotherapy Alone
Anja Thronicke1; Thomas Reinhold2; Philipp von Trott3; Harald Matthes2,4,5;
Friedemann Schad1,3
1Research Institute Havelhöhe, Berlin, Deutschland
2Institute of Social Medicine, Epidemiology and Health Economics, Charité
Universitätsmedizin Berlin, Berlin, Deutschland
3Oncological Centre, Interdisciplinary Oncology and Supportive Medicine,
Gemeinschaftskrankenhaus Havelhöhe, Berlin, Deutschland
4Medical Clinic for Gastroenterology, Infectiology and Rheumatology, Charité
Universitätsmedizin Berlin, Berlin, Deutschland
5Gastroenterology, Gemeinschaftskrankenhaus Havelhöhe, Berlin, Deutschland
Purpose: Improved overall survival (OS) has been observed in late stage
cancer patients receiving add-on Viscum album L. treatment [1, 2]. e
objective of the present study was the cost-eectiveness analysis (CEA) for
chemotherapy plus add-on Viscum album L (V) compared to chemothera-
py alone (C) in patients with stage IV lung cancer.
Methods: A real-world study was conducted (DRKS00013335). Patients
with stage IV lung cancer received C or V treatment in a certied Ger-
man Cancer Centre. Cost analyses and CEA (hospital’s perspective) were
performed.
Results: 118 patients (C: n=86, V: n=32) were included (mean age 63.8 y,
55% male). Adjusted hospitals mean costs were €16,288.98 for C (over an
adjusted mean OS time of 13.4m) and €17,992.26 for V (over an adjusted
mean OS time of 19.1m), respectively. Hospital’s savings of €273.60 per
mean month OS in the V-group were observed compared to C. e costs
per additionally gained OS year with the V-treatment compared to C were
€3,585.84 (ICER).
Conclusions: e stationary costs per mean OS month were lower for the
combinational V- compared to the C-treatment alone. Further prospec-
tive and randomized studies are mandatory.
References:
1. Tröger W et al. European Journal of Cancer, 2013
2. Schad F et al. PLoS One, 2018.
Disclosure: Grants from Helixor Heilmittel GmbH (FS). Administrative board
Weleda AG (HM). No competing interests (AT, TR, PVT).
934
Ecacy of Docetaxel/Ramucirumab as Palliative Third-Line
Therapy Immediately after Second-Line Immune-Checkpoint
Inhibitor (ICI) Treatment in Patients with Non-Small Cell Lung
Cancer (NSCLC) UICC Stage IV
Wolfgang Brückl1; Achim Rittmeyer2; Jens Kollmeier3; Claas Wesseler4;
Gunther Wiest4; Martin Reck5; Michael Thomas6; Petros Christopoulos6;
Amanda Tufman7; Petra Hoknecht8; Bernahard Ulm9; Fabian Reich1;
Joachim Ficker1; Heinz-Eckart Laack10
1Medizinische Klinik 3, Klinikum Nürnberg, Nürnberg, Deutschland
2Klinikum Immenhausen
3Helios Kliniken Berlin
4Asklepios Klinik Harburg
5Klinikum Grosshansdorf, Großhansdorf, Deutschland
6Thoraxklinik-Heidelberg gGmbH, Heidelberg, Deutschland
7LMU München
8Franziskus-Hospital Harderberg, Georgsmarienhütte, Deutschland.
9TU München Institut für Statistik
10Hämato-Onkologie Hamburg, Prof. Laack und Partner, Hamburg, Deutschland
Background: Antiangiogenic agents have shown to stimulate the immune
system and cause synergistic eects in combination with chemotherapy.
is eect might be even stronger aer immune-checkpoint-inhibitor
(ICI) therapy. erefore, we conducted a retrospective analysis to evaluate
the ecacy of ramucirumab plus docetaxel (ram+doce) as 3rd line treat-
ment aer failure of platinum-based combination and ICI in patients with
NSCLC stage UICC IV in 1st and 2nd line, respectively.
Methods: 67 patients with non-small cell lung cancer (NSCLC), starting
their palliative 1st line treatment between 3/13 and 9/18 could be collected
from nine German high-volume oracic Oncology Centers. All patients
were treated by the same kind of 1st and 2nd line therapy and received at
least one cycle of 3rd line therapy with ram+doce. e numbers of cycles,
response rate, PFS to 3rd line treatment and OS were investigated aer a
positive IRB vote.
Results: e median age of patients was 62 (range: 42-82) years with 69%
of the patients being male. e histology was adenocarcinoma, squamous
cell carcinoma and other in 58%, 36% and 6%, respectively. Due to 3rd
line, the mean number of ramucirumab cycles was 6.5 (95%CI: 5.3-7.7)
with a mean number of 3.5 cycles given as a combination treatment. e
ORR to ram+doce was 36% and DCR of 69%. More patients received a
response to 3rd line as to 2nd line with 11% having a response to both
lines. mPFS was 6.8 months (95%CI:4.6-9.0) with a DOR of 10.2 months
(95%CI: 9.3-11.1). e mOS from starting with 3rd line therapy was 11
months (95%CI: 7.1-14.9). With 17 patients (25%) receiving further treat-
ment in 4th line the mOS was 29 months (95%CI: 25.4-32.8). Concerning
histology, there was no dierence between adenocarcinoma and squa-
mous cell carcinoma for the PFS results. Additionally, no new AE were
reported.
Conclusions: Ram+doce showed encouraging eectivity in 3rd line ther-
apy immediately aer failure of 2nd line ICI and can be used irrespectively
of NSCLC histology. Eectivity aer ICI plus chemotherapy in 2nd line
treatment is actually analyzed in a separate cohort.
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948
Entrectinib in Locally Advanced / Metastatic ROS1 and NTRK
Fusion-Positive (NTRK+) Non-Small Cell Lung Cancer (NSCLC):
Updated Integrated Analysis of STARTRK-2, STARTRK-1 and
ALKA-372-001
Christoph Springfeld1; Filippo de Braud2,3; Salvatore Siena3,4;
Fabrice Barlesi5; Alexander Drilon6; Brian Simmons7; Xinhui Huang8;
Bethany Pitcher9; Robert C. Doebele10
1Department of Medical Oncology, Universität Heidelberg, National Center for
Tumor Diseases, Heidelberg, Deutschland
2Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto
Nazionale dei Tumori, Milano, Italien
3Department of Oncology and Hemato-Oncology, Università degli Studi di
Milano, Milano, Italien
4Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano,
Italien
5Multidisciplinary Oncology & Therapeutic Innovations Department, Aix-
Marseille Univeristy, Marseille, Frankreich
6Thoracic Oncology Service, Division of Solid Tumor Oncology, Department
of Medicine , Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical
College, New York, NY, United States
7Genentech, Inc., South San Francisco, United States
8Genentech, Inc., South San Francisco, CA, United States
9F. Homann- La Roche, Basel, Schweiz
10Division of Medical Oncology, University of Colorado Cancer Center, Aurora,
CO, United States
Purpose: Entrectinib is a systemic and central nervous system (CNS)-ac-
tive potent inhibitor of ROS1 and TRKA/B/C. Primary data showed that
entrectinib was tolerable and achieved high objective response rates (ORR)
in patients (pts) with ROS1-positive (ROS1+), ROS1 inhibitor-naïve NS-
CLC, and in pts with NTRK+ NSCLC, including pts with baseline CNS
disease. We present data from an additional 5 mo follow-up.
Methods: Pts with locally advanced/metastatic ROS1+ or NTRK+ tumors
(with or without baseline CNS disease) conrmed by nucleic acid-based
methods, enrolled in global Phase 1/2 entrectinib trials (ALKA-372-001
[EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2
[NCT02568267]) were included. Disease burden was assessed per blinded
independent central review (BICR) using RECIST v1.1, aer 4 wks (Cy-
cle 1), then every 8 wks. Primary endpoints were ORR and duration of
response (DOR) by BICR. Secondary endpoints included ORR and DOR
in pts with or without baseline CNS disease, and safety. Intracranial (IC)
ORR and DOR were evaluated in pts with baseline CNS disease.
Results: ere were 53 ecacy-evaluable pts with treatment-naïve,
ROS1+ NSCLC and 10 pts with NTRK+ NSCLC. As of Oct 30, 2018 (addi-
tional 5 mo follow-up), BICR ORR: ROS1+ 79.2% (95% CI 65.9–89.2) and
NTRK+ 70.0% (95% CI 34.75–93.33) with complete responses in 5 (9.4%)
pts and 1 (10.0%) pt, respectively. In ROS1+ NSCLC, median DOR: 24.6
mo (95% CI 12.6–34.8); in pts with and without baseline CNS disease,
ORR was 73.9% (95% CI 51.6–89.8) and 83.3% (95% CI 65.3–94.4); IC
ORR was 55.0% (95% CI 31.5–76.9); and median IC DOR was 12.9 mo
(95% CI 5.6–not estimable). Additional ecacy for NTRK+ NSCLC pts
will be presented. Entrectinib was well tolerated, with a safety prole con-
sistent with that previously reported; there were no new or unexpected
safety ndings.
Conclusions: In line with the primary data, in pts with ROS1+ and
NTRK+ NSCLC, aer an additional 5 mo follow-up, entrectinib was well
tolerated, and showed clinically meaningful, durable systemic and intra-
cranial responses.
992
Entrectinib in Patients with NTRK Fusion-Positive Solid
Tumors or ROS1-Positive NSCLC with CNS Metastases
Luis Paz-Ares1; Rafal Dziadziuszko2; Alexander Drilon3; Thomas John4;
Matthew Krebs5,6; George Demetri7; Alice T. Shaw8; Salvatore Siena9,10;
Jürgen Wolf11; Anna F. Farago8; Brian Simmons12; Bethany Pitcher13;
Xinhui Huang12; Robert Doebele14
1Department of Medical Oncology, Hospital Universitario 12 de Octubre,
Madrid, Spanien
2Department of Oncology and Radiotherapy, Medical University of Gdansk,
Gdansk, Poland
3Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill
Cornell Medical College, New York, NY, United States
4Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer &
Wellness Centre, Melbourne, Australien
5Division of Cancer Sciences, The University of Manchester NIHR Clinical
Research Facility, The Christie NHS Foundation Trust, Manchester, United
Kingdom
6NIHR Manchester Biomedical Research Centre (BRC), Manchester, United
Kingdom
7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA,
United States
8Center for Thoracic Cancers, Massachusetts General Hospital, Boston, MA,
United States
9Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda,
Milan, Italien
10Department of Oncology and Hemato-Oncology, Università degli Studi di
Milano, Milan, Italien
11Center for Integrated Oncology, University Hospital of Cologne, Cologne,
Deutschland
12Genentech, Inc., South San Francisco, CA, United States
13F. Homann La-Roche, Basel, Schweiz
14Division of Medical Oncology, University of Colorado Cancer Center, Aurora,
CO, United States
Purpose: Entrectinib potently inhibits kinases encoded by NTRK and
ROS1 genes. It achieves therapeutic levels in the CNS with antitumor ac-
tivity in intracranial tumor models. We report an integrated analysis data
(May 31, 2018 data cut-o) from three Phase 1/2 entrectinib trials (ALKA-
372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810];
STARTRK-2 [NCT02568267]) for a large cohort of adult patients.
Methods: Patients had locally advanced/metastatic NTRK+ solid tumors
or ROS1+ NSCLC conrmed by nucleic acid-based assays. Baseline CNS
metastases were identied by CT/MRI. Tumor assessments were per-
formed at baseline, week 4, and then every 8 weeks by BICR (RECIST
v1.1). Primary endpoints were overall response rate and duration of re-
sponse. Secondary endpoints included progression-free survival, overall
survival, intracranial ecacy in patients with CNS metastases, and safety.
Results: Most patients were treated rst-line or aer one line of prior
therapy. CNS lesions at baseline were observed in 22.2% of NTRK+ solid
tumors (n=54; 18% NSCLC) and 43.4% of ROS1+ NSCLC (n=53), with
58.3% and 65.2% of these having received prior radiotherapy. Intracra-
nial ORR was 54.5 (95% CI 23.4–83.3) for NTRK+ and 55.0 (31.5–76.9)
for ROS1+ NSCLC. Durability of treatment eect and potential delayed
progression in the CNS was observed; Time to CNS progression was 17.0
months (95% CI 14.3–NE) for NTRK+ solid tumor patients and NE (95%
CI 15.1–NE) for ROS1+ NSCLC. Median duration of response was NE
(5.0–NE) and 12.9 (5.6–NE) for NTRK+ and ROS1+ NSCLC, respective-
ly. In the subset of patients with NTRK+ NSCLC (n=10), 6 patients had
CNS metastases at baseline (by BICR); IC-ORR was 66.7% (4/6), 2 CR;
IC-DOR was NE. In both the NTRK+ and ROS1+ populations, entrectinib
was tolerable with a manageable safety prole; most treatment-related
AEs were grade 1–2.
Conclusions: Entrectinib induced clinically meaningful durable respons-
es in patients with NTRK+ solid tumors or ROS1+ NSCLC with CNS dis-
ease at baseline.
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Inhalt
2018
Index
2018
1000
Nivolumab (NIVO) Plus Low-Dose Ipilimumab (IPI) as First-
Line (1L) Treatment (tx) of Advanced Nsclc: Overall Survival
(Os) Analysis of Checkmate 817
Jürgen R. Fischer1; Fabrice Barlesi2; Clarisse Audigier-Valette3;
Enriqueta Felip4; Tudor-Eliade Ciuleanu5; Kevin Jao6; Erika Rijavec7;
Laszlo Urban8; Jean-Sébastien Aucoin9; Cristina Zannori10;
Karim Vermaelen11; Osvaldo Aren Frontera12; Neal Ready13;
Alessandra Curioni Fontecedro14; Helena Linardou15;
Elena Poddubskaya16; Rathi Pillai17; Sunney LI18; Angelic Acevedo18;
Luis Paz-Ares19
1Löwenstein Clinic gGmbH, Löwenstein, Deutschland
2Aix-Marseille Université; CNRS, INSERM, CRCM; Assistance Publique-Hôpitaux
de Marseille (APHM), Marseille, Frankreich
3Hôpital Sainte-Musse, Toulon, Frankreich
4Vall d’Hebron University Hospital, Barcelona, Spanien
5The Oncology Institute Ion Chiricuta and University of Medicine and Pharmacy
Iuliu Hatieganu, Cluj-Napoca, Romania
6Hôpital du Sacré-Cœur de Montréal, Montreal, Kanada
7Lung Cancer Unit, Istituto di Ricovero e Cura a Carattere Scientico (IRCCS)
Ospedale Policlinico San Martino, Genova, Italien
8Matrahaza University and Teaching Hospital, Matrahaza, Ungarn
9Centre Intégré Universitaire de Santé et de Services Sociaux de la Mauricie-
et-du-Centre-du-Québec, Trois-Rivières, Kanada
10Azienda Ospedaliera Santa Maria di Terni, Terni, Italien
11Ghent University Hospital, Ghent, Belgien
12Centro Internacional de Estudios Clinicos, Santiago, Chile
13Duke Cancer Center, Durham, United States
14Department of Medical Oncology and Hematology, University Hospital Zurich,
Zurich, Schweiz
15Oncology Unit, Metropolitan Hospital, Athens, Griechenland
16VitaMed LLC, Moscow, Russland
17Winship Cancer Institute, Atlanta, United States
18Bristol-Myers Squibb, Princeton, United States
19Hospital Universitario 12 de Octubre, Madrid, Spanien
Purpose: NIVO + IPI showed improved OS vs chemotherapy as 1L tx
for advanced NSCLC with tumor programmed death ligand 1 (PD-L1)
≥ 1% and < 1% in CheckMate 227. CheckMate 817 (NCT02869789) is
a multi-cohort, single arm, phase 3b study evaluating at-dose NIVO +
weight-based low-dose IPI in advanced NSCLC. Preliminary safety and
ecacy results were previously reported for cohorts A and A1. We present
additional safety data and OS in these cohorts.
Methods: Patients (pts) with previously untreated stage IV or recurrent
NSCLC, and no known sensitizing EGFR or ALK alterations, were eligi-
ble regardless of PD-L1 expression. Cohort A (n = 391) had ECOG per-
formance status (PS) 0–1; cohort A1 (special populations; n = 198) had
ECOG PS 2 or a specied comorbidity (asymptomatic untreated brain
metastases, hepatic or renal impairment, or HIV). Pts were treated with
NIVO 240 mg Q2W + low-dose IPI 1 mg/kg Q6W for 2 y or until disease
progression/unacceptable toxicity. Safety in cohort A was the primary
endpoint; ecacy endpoints were secondary/exploratory; A1 safety and
ecacy analyses were exploratory.
Results: Baseline characteristics, except ECOG PS and comorbidities,
were similar between cohorts. With minimum follow-up of 21 mo (A) and
14 mo (A1), median OS was 17.0 mo and 9.9 mo, respectively. At 1 y, 60%
(A) and 47% (A1) of pts were alive. OS by PD-L1 expression and tumor
mutational burden levels will be presented. e safety prole (type and
rate of treatment-related adverse events [TRAEs]) was consistent between
the cohorts. e range of median time to onset of select TRAEs was 2–26
wk (A) and 2–21 wk (A1). Most select TRAEs had resolved (40%–100%).
Conclusions: e select TRAE prole of NIVO + low-dose IPI was simi-
lar between cohorts A and A1. Durable OS outcomes were observed with
1L NIVO + IPI in pts with advanced NSCLC (cohort A) and were com-
parable with CheckMate 227; although as expected, comorbidities and/or
poor PS impacted outcomes in cohort A1.
Disclosure Statement:
Funding: BMS
Previously presented at ESMO I-O 2019, FPN 92O, Barlesi et al. Reused
with permission.
1009
Final Progression-Free Survival (PFS), Updated Overall
Survival (OS), And Safety Data from the Global, Randomized,
Phase 3 Alex Study of Alectinib (ALC) Versus Crizotinib (CRZ)
in Untreated Advanced ALK+ Non-Small Cell Lung Cancer
(NSCLC)
Petra Hoknecht1; Tony Mok2; Alice T. Shaw3; D. Ross Camidge4;
Shirish Gadgeel5; Rafael Rosell6; Rafal Dziadziuszko7; Dong-Wan Kim8;
Maurice Perol9; Sai-Hong Ou10; Walter Bordogna11; Vlatka Smoljanovic11;
Magalie Hilton11; Solange Peters12
1Niels-Stensen-Kliniken, Osnabrück, Deutschland
2State Key Laboratory of Translational Oncology, Chinese University of Hong
Kong, NT, Hong Kong
3Massachusetts General Hospital, Boston, MA, United States
4University of Colorado, Denver, CO, United States
5Department of Internal Medicine, Rogel Cancer Center/University of Michigan,
Ann Arbor, MI, United States
6Catalan Institute of Oncology, Barcelona, Spanien
7Department of Oncology and Radiotherapy, Medical University of Gdansk,
Gdansk, Poland
8Seoul National University Hospital, Seoul, Südkorea
9Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, Frankreich
10Chao Family Comprehensive Cancer Center, University of California, Irvine,
United States
11F. Homann-La Roche Ltd, Basel, Schweiz
12University Hospital of Vaudois (CHUV), Lausanne, Schweiz
Purpose: To report mature PFS, updated OS, and safety from the ALEX
study (NCT02075840) aer a further 12 months (m) of follow-up (FU;
cuto: 30/11/18).
Methods: Pts had stage IIIB/IV ALK+ NSCLC (central IHC), ECOG PS
0–2, and no prior systemic therapy for advanced NSCLC. Asymptomatic
CNS mets were allowed. Pts were randomized 1:1 to bid ALC 600 mg
(n=152) or CRZ 250 mg (n=151). Primary endpoint: investigator-assessed
PFS (INV-PFS; RECIST v1.1), with q8w CNS imaging in all pts.
Results: Mature median INV-PFS: 34.8 m (95% CI 17.7–NR) ALC v 10.9
m (95% CI 9.1–12.9) CRZ (ITT stratied HR 0.43, 95% CI 0.32–0.58;
p<0.0001); events: 53.3% ALC v 80.8% CRZ. Median FU: 37.8 m ALC v
23.0 m CRZ. Median INV-PFS was longer with ALC v CRZ in pts with
baseline (BL) CNS mets (25.4 m v 7.4 m, HR 0.37, 95% CI 0.23–0.58)
and in those without (38.6 m v 14.8 m, HR 0.46, 95% CI 0.31–0.68). PFS
event-free rate was higher with ALC v CRZ regardless of BL CNS mets. %
PFS event-free rates (95% CI; ALC v CRZ): 1 year: 67.8 (60.3–75.3) v 48.0
(39.7–56.2); CNS mets: 58.5 v 32.5; no CNS mets: 74.5 v 57.2; 2 years: 56.6
(48.6–64.6) vs 24.8 (17.6–32.1), CNS mets: 52.0 v 6.3; no CNS mets: 59.8 v
35.7; 3 years: 46.4 (38.2–54.5) v 13.5 (7.7–19.3); CNS mets: 40.5 v 2.1; no
CNS mets: 50.6 v 20.2; 4 years: 43.7 (35.4–51.9) v not estimable (NE); CNS
mets: 38.0 v NE; no CNS mets: 47.6 v NE. OS data remain immature (ALC
events: 32%; stratied HR 0.69, 95% CI 0.47–1.02). OS in pts with BL CNS
mets, HR 0.60 (95% CI 0.34–1.05) and in pts without BL CNS mets, HR
0.77 (95% CI 0.45–1.32). % OS event-free rates (ALC v CRZ): 1 year: 84.3
(78.4–90.2) v 82.5 (76.1–88.9); 2 years: 72.5 (65.1–79.9) v 65.1 (56.7–73.4);
3 years: 66.9 (59.0–74.8) v 56.7 (47.8–65.6); 4 years: 64.5 (55.6–73.4) v 52.2
(42.6–61.8).
Considering the longer median treatment duration with ALC v CRZ
(27.7 m v 10.8 m), the safety prole for ALC remains favorable; fewer
ALC-treated pts experienced grade 3–5 adverse events (48.7% v 55.0%).
Conclusions: is nal updated PFS analysis conrms the superior e-
cacy and favorable tolerability of ALC v CRZ in pts with untreated ALK+
NSCLC. OS data remain immature.
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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 237
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2018
Index
2018
1015
Characterization of Lung Cancer Cell Lines by Single Cell
Analysis
Frauke Sophie Seeber1; Anna Hinze1; Andreas Hochhaus1;
Joachim Clement1
1Abt. Hämatologie und Internistische Onkologie, Universitätsklinikum Jena,
Jena, Deutschland
Purpose: Lung cancer is the most common and most deadly form of
cancer with a prevalence of 11.6% and 1.7 million cancer related deaths
worldwide [1]. Primary tumors consist of millions of cells which show
distinct morphological and phenotypical dierences. ese dierences
are even more evident between cells related to the primary tumor and
cells related to metastasis. Tumor heterogeneity is highly associated with
acquired drug resistance. e elucidation of cell-to-cell heterogeneity is a
major challenge but will be helpful to improve personalized therapy. To
face this challenge, we intent to use single cell analysis to better under-
stand tumor heterogeneity and thus improve cancer diagnosis and treat-
ment design.
Materials and methods: e lung cell lines A549 and 103H were used
for single cell analysis. e cell line A549 represents adenocarcinoma
and 103H large cell lung carcinoma. Both were cultivated and prepared
to isolate single cells with the CellCelectorTM. Aer cell lysis DNA and
mRNA were prepared simultaneously [2].e quality of prepared DNA
and mRNA was validated using selected DNA-sequences or housekeep-
ing-genes. KRAS mutation analysis (34G>A) was performed by pyrose-
quencing. Expression levels of BIRC5 and STK11 were determined by
qPCR.
Results: 64 A549 single cells and 56 103H single cells were isolated, as
well as 56 single leukocytes for control. Pyrosequencing revealed that 47%
of A549 single cells exhibit the homozygous KRAS mutation (34G>A),
whereas no 103H cell or leukocyte showed neither homozygous nor het-
erozygous mutations. Regarding the expression of BIRC5 A549 and 103H
showed a robust expression, whereas leukocytes expression levels were
below detection limit. In contrast, the expression level of STK11 was com-
parable in all cell types tested.
Conclusion: e detection of KRAS mutation 34G>A in single cells con-
rms the potential of this approach to screen for genomic alterations in
rare cells, e.g. circulating tumor cells, as well as for expression patterns.
1. Editorial (2019) e Lancet 294:1880
2. Klein et al. (2002) Nat Biotechnol 20:387-392
1042
Tumor PD-L1 Expression in Stage III NSCLC: Initial Biomarker
Results from the German Intergroup Lung Trial (GILTCTRT)
Amanda Tufman1; Jens Neumann2; Andreas Jung2;
Diego Kaumann-Guerrero1; Farkhad Manapov3; Pontus Mertsch1;
Laura Sellmer1; Bernahard Ulm4; Kurt Ulm4; Stefan Andreas5;
Michael Flentje6; Rudolf M. Huber1
1Klinikum der LMU München, Medizinische Klinik V, München, Deutschland
2Ludwig-Maximilians Universität, Institut für Pathologie, München, Deutschland
3Klinik und Poliklinik für Strahlentherapie, Klinikum der Universität München,
München, Deutschland
4Technische Universität München, Institut für Statistik, München, Deutschland
5Lungenfachklinik Immenhausen, Zentrum für Pneumologie, Immenhausen,
Deutschland
6Universitätsklinikum Würzburg, Klinik und Poliklinik für Strahlentherapie,
Würzburg, Deutschland
Purpose: PD-L1 expression may predict benet from PD-L1 inhibition
following radiochemotherapie (RTCT). e multicenter German Inter-
group Lung Trial (GILT) randomised patients with inoperabel stage III
NSCLC to RTCT with or without consolidation chemotherapy. We ana-
lysed immune markers in biopsies from the GILT trial, investigating the
prognostic role of PD-L1 and tumor inltrating lymphocytes (TiL) in this
setting.
Methods: We retrospectively collected biopsies from patients treated in
the GILT trial. PD-L1 expression was analysed using the Ventana SP263
assay. e primary endpoint of these analyses was PFS following RTCT
in patients with PDL-1 positive (IHC ≥ 1% PDL-1) vs. PDL-1 negative
(IHC<1% PDL-1) NSCLC. Secondary endpoints explored additional PD-
L1 cut-os, TiLs (score and pattern), driver mutations, and the markers
CD3 and FOXP3. Here we present results of PD-L1 expression scores.
Results: 279 patients were included in the GILT study; biopsies were
available from 95 patients. ose with available samples were similar to
the whole study population in age, gender, histology and stage. PD-L1
scores from 61 samples were available for this initial analysis: 22 samples
showed no PD-L1 expression and 39 showed expression in ≥ 1% of tumor
cells. ere was no PFS-dierence in PD-L1 0 vs. PD-L1 ≥ 1% subgroups.
An exploratory cut-o of 20% PD-L1 expression showed a slight trend to
improved PFS with PD-L1 ≥ 20%.
Conclusions: In biopsies from the large, randomised GILT study, PD-L1
did not correlate signicantly with PFS following RTCT. Further analyses
to explore the eect of TiLs, mutations and other immune cell populations
are planed.
Disclosure Statement: IIT funding from AstraZeneca
1049
First Description of an Unknown Anaplastic Lymphoma Kinase
(ALK) Exon 23 Mutation Following Treatment with Alectinib in
a Patient with Metastatic Non-Small Cell Lung Cancer (NSCLC)
Georg Evers1; Michael Mohr1; Wolfgang Hartmann2; Arik Schulze1;
Christoph Schülke3; Annalen Bleckmann1
1Medizinische Klinik A, Universitätsklinikum Münster, Münster, Deutschland
2Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster,
Münster, Deutschland
3Institut für Klinische Radiologie, Universitätsklinikum Münster, Münster,
Deutschland
Purpose: Rearrangements of the ALK gene are harbored in 3 to 5% of NS-
CLC patients. e presence of genetic driver mutations enables the use of
targeted therapies with tyrosine kinase inhibitors (TKIs). Following TKI
therapy disease progression can occur due to new resistance mutations.
Against this background, molecular genetic testing using tissue or liquid
biopsy is increasingly used. However, knowledge of second line TKI eec-
tiveness on resistance mutations has only been gained from in vitro data
and the actual eect on tumor growth therefore remains unclear. Here we
present our case report of a rare resistance mutation following treatment
with Alectinib.
Methods: To highlight molecular testing using next generation sequenc-
ing (NGS) and to describe an unknown ALK-mutation we present a case
report with clinical, radiological and molecular genetic data.
Results: Following detection of chromosome 2p23 ALK translocation, a
65-year old patient with metastatic NSCLC was successfully treated with
Alectinib over a period of 20 months. Due to hepatic disease progression
tissue sampling was subsequently performed. Using NGS the p.A1200_
G1201delinsW mutation in exon 23 of the ALK-gene was detected in both
liquid and tissue biopsy. is mutation is in close proximity to the well-
known G1202R mutation and has not been described so far in literature.
erapy with the second generation ALK-inhibitor Brigatinib was started,
interestingly leading to complete resolve of B-symptoms and to a radio-
logically proven stable disease.
Conclusions: Disease progression aer rst line TKI therapy entails the
need for renewed tumor tissue sampling with genetic testing. Of inter-
est, detection of the p.A1200_G1201delinsW mutation in exon 23 of the
ALK-gene has not yet been described. Treatment with the next generation
ALK-inhibitor Brigatinib may be a potential treatment option when this
mutation is detected. erefore, aer rst line TKI therapy, further ALK
inhibition should also be considered, even if unknown resistance muta-
tions occur.
References:
Disclosure Statement: Nothing to declare
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2018
Index
2018
Lymphoma and Plasma Cell Disorders
Vorträge
963
Magnify: A Phase IIIB Trial Shows Promising Ecacy in the
Treatment of Relapsed/Refractory, Indolent Non-Hodgkin
Lymphoma Patients with Lenalidomide in Combination with
Rituximab (R²)
Mathias Rummel1; David J. Andorsky2; Burkhard Schmidt3; Paul La Rosée4;
Ullrich Graeven5; Myron Czuczman6; Mary Llorente6; Jiahui LI6;
Je Sharman7
1Medizinischen Klinik IV und V, Justus-Liebig Universität, Giessen, Deutschland
2Rocky Mountain Cancer Centers, US Oncology Research, Boulder, CO, United
States
3Hämato-Onkologische Überörtliche Gemeinschaftspraxis Pasing und
Fürstenfeldbruck, München-Pasing, Deutschland
4Klinik für Innere Medizin II, Schwarzwald-Baar Klinikum, Villingen-
Schwenningen, Deutschland
5Klinik für Hämatologie, Onkologie und Gastroenterologie, Kliniken Maria Hilf
GmbH, Mönchengladbach, Deutschland
6Bristol-Myers Squibb, Summit, NJ, United States
7Willamette Valley Cancer Institute and Research Center, US Oncology Research,
Eugene, OR, United States
Purpose: Standard treatment is lacking in relapsed/refractory (R/R) indo-
lent NHL (iNHL), as indicated by a median PFS of <1 y with PI3K inhib-
itors. Recently, the immunomodulatory agent lenalidomide (L) reported
enhanced activity with rituximab (R) as combination R2, with a median
PFS of 39.4 mo in R/R iNHL patients (pts; AUGMENT: Leonard et al. J
Clin Oncol; 2019.).
Methods: e global, multicenter, non-registrational, randomized phase
IIIb MAGNIFY trial was designed to determine the optimal duration of
R2 in pts with R/R FL gr 1-3a and MZL (NCT01996865). R2 treatment is
12 cycles of L (20 mg/d, d1-21/28) + R (375 mg/m2/wk cycle 1 and every
8 wk for cycles 3+) followed by 1:1 randomization in patients with stable
disease or better to continue with R2 vs R maintenance. e interim pri-
mary endpoint was overall response rate (ORR) by 1999 IWG criteria with
induction R2 in treated, ecacy-evaluable pts with baseline/post-baseline
assessments.
Results: At a median 16.7-mo follow-up (range, 0.39-48.8), 370 pts (295
[80%] FL gr 1-3a; 75 [20%] MZL) were enrolled with a median age of
66 y, 83% stage III/IV disease, and a median of 2 prior therapies (range,
1-11; 95% prior R-containing). Ecacy-evaluable pts showed a 73% ORR
and 45% CR. Median TTR was 2.7 mo, median DOR was 36.8 mo, and
median PFS was 36.0 mo (overall) and 18.1 mo (rituximab-refractory).
e most common all-grade AEs were 48% fatigue, 40% neutropenia, 35%
diarrhea, 30% nausea, and 29% constipation. Grade 3/4 neutropenia was
34%; all other grade 3/4 AEs were <6%. ese results are corroborated
by the AUGMENT trial, in which a total of 358 pts with R/R FL gr 1-3a
and MZL were randomized to R2 (n=178) vs placebo/rituximab (n=180),
where PFS was signicantly improved for R2 with a HR of 0.46 (95% CI,
0.34-0.62; P<0.001) and median PFS of 39.4 mo (95% CI, 22.9 mo-NR) vs
14.1 mo (95% CI, 11.4-16.7), respectively.
Conclusions: L improves the ecacy of R, as shown by a clinically active
(with a high CR rate) and well tolerated R2 therapy in pts with recurrent
indolent lymphoma, including those refractory to rituximab.
Pediatric Cancer
Poster
501
Associated Factors to Reduced Physical Activity in Long-Term
Childhood Cancer Survivors in Germany
Marie Astrid Neu1; Sandra Stössel1; Arthur Wingerter1; Andreas Schulz2;
Nicole Henninger1; Hiltrud Merzenich3; Maria Blettner3; Norbert Pfeier4;
Thomas Münzel5; Jürgen Prochaska2,6,7,8; Philipp Wild2,6,7,8; Astrid
Schneider3; Joerg Faber1
1Childhood Cancer Center , University Medical Center Mainz, Deutschland
2Preventive Cardiology and Preventive Medicine, University Medical Center
Mainz , Deutschland
3Institute for Medical Biostatistics, Epidemiology and Informatics, University
Medical Center Mainz , Deutschland
4Department of Ophthalmology , University Medical Center Mainz ,
Deutschland
5Center for Cardiology , University Medical Center Mainz , Deutschland
6German Center for Cardiovascular Research Partner Site Rhine-Main,
Deutschland
7Center for Thrombosis and Haemostasis, University Medical Center Mainz ,
Deutschland
8Center for Translational Vascular Biology, University Medical Center Mainz ,
Deutschland
Purpose: Based on the “Cardiac and vascular late sequelae in long-term
survivors of childhood cancer (CVSS)-study”, the physical activity (PA)
level in German childhood cancer survivors (CCS) was evaluated in rela-
tion to tumor entity and compared to the general population.
Methods: In this cross-sectional study, 1002 CCS diagnosed with neopla-
sia prior to 15 years of age between 1980 and 1990 were recruited. Level
of PA was determined by questionnaire. An activity score (AS) was then
calculated based on reported intensity and time of PA and compared to
the population-based Gutenberg Health Study (GHS) cohort. Participants
were 23 to 50 years old.
Results: In total, physical activity questionnaire data was available from
951 CCS and compared to data from 5497 GHS participants. Aer adjust-
ing for sex and age, results from multiple linear regression model revealed
that AS was 24% lower in CCS than in GHS participants (-0.24 (95% CI
-0.32 to -0.15); p<0.0001). With regard to tumor entity, AS was lower in
CCS from leukemia (-0.18 (95% CI -0.29 to -0.072; p=0.0012), central
nervous system tumor (-0.39 (95% CI -0.57 to -0.20), p=0.0001), renal
tumor (-0.27 (95% CI -0.50 to -0.043); p=0.020), so tissue sarcoma (-0.34
(95% CI -0.58 to -0.10); p=0.0052) and malignant bone tumor (-0.54 (95%
CI -0.81 to -0.26); p=0.00014) compared to GHS participants. However, in
CCS from lymphoma, neuroblastoma and germ cell tumor, there was no
signicant dierence in AS compared to GHS participants. Furthermore,
no association of AS was found in relation to chemotherapy, radiotherapy,
recurrence rate and age at diagnosis among CCS.
Conclusions: In the present study, reduced PA level in German CCS was
associated to tumor entity. Based on these ndings, future investigations
should explore potential benets of adapted exercise programs on PA be-
havior and associated physical and mental wellbeing.
Reference:
1. PMID: 10993420; PMID: 29534171
Disclosure Statement: Nothing to disclose
e abstract was also submitted for the 8th Annual Meeting of Exercise is
Medicine in Europe, September 20-21, 2019, Amsterdam
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941
Mental Health and Health-Related Quality of Life in
Young Survivors of Early Childhood Cancer. Results of the
Prospective Cohort Study IKIDS-OEVA
Marie A. Neu1; Jennifer Schlecht2; Martina F. Schmidt2;
Abigale Luise Robinson1; Claudia Spix3; Peter Kaatsch3; Jörg Faber1;
Michael S. Urschitz2; For the Ikids Study Group
1Department of Pediatric Hematology/Oncology/Hemostaseology, Center for
Pediatric and Adolescent Medicine, University Medical Center Mainz, Mainz,
Deutschland
2Division of Pediatric Epidemiology, Institute of Medical Biostatistics,
Epidemiology and Informatics (IMBEI), University Medical Center Mainz, Mainz,
Deutschland
3German Childhood Cancer Registry (GCCR), Institute of Medical Biostatistics,
Epidemiology and Informatics (IMBEI), University Medical Center Mainz, Mainz,
Deutschland
Purpose: Long-term survivors of childhood cancer are at increased risk
for sequelae as poor mental health (MH) or health-related quality of life
(HrQoL). We aimed to evaluate early adverse eects on MH and HrQoL
in preschool survivors of early childhood cancer.
Methods: A nationwide prospective cohort study was performed. Chil-
dren aged 5 or 6 years with an oncological disease at preschool age (OEVA,
excluding brain tumors) and completed cancer treatments were identied
in the German Childhood Cancer Registry and approached. e compar-
ison group were children of the same age without oncological disease who
participated in the prospective population-based health survey ikidS. In
both groups, children with expected delayed school enrollment were ex-
cluded. MH problems and HrQoL were assessed by parental versions of
the Strengths and Diculties (SDQ) and the KINDL questionnaires, re-
spectively. Children with other chronic health conditions were identied
by the Children with Special Health Care Needs screener. e associations
between OEVA and MH problems as well as HrQoL were analyzed by
linear regression adjusted for potential confounders.
Results: Of 382 children with OEVA contacted, 145 were enrolled, and
124 analyzed (48% boys, mean age at diagnosis 2.4 y). Compared to chil-
dren without OEVA (3683 contacted, 2003 enrolled, 1422 analyzed), chil-
dren with OEVA had more MH problems (13% vs. 3%) and slightly poorer
HrQoL (median 78.7 vs. 80.2 points). In the adjusted analysis, children
with OEVA had higher SDQ scores (adjusted mean dierence 2.2, 95%CI
[1.3; 3.0]; P<0.001) and lower KINDL scores (adjusted mean dierence
-2.4, 95%CI [-3.7; -1.1]; P<0.001) compared to children who had neither
OEVA nor a special health care need.
Conclusions: Childhood cancer survivors at preschool age may be at
increased risk of MH problems and poorer HrQoL. is could have an
impact on subsequent educational attainment. Follow-up health care for
OEVA survivors should include early screening for MH problems and
other HrQoL decits.
References:
1. PMID:29584786.
Disclosures: No conict of interest.
968
Sports Therapy in Pediatric Oncology at the Childrens
Hospital Munich Schwabing – Results after 3,5 Years of
Interdisciplinary Collaboration
Dominik Gaser1,2; Sabine Kesting1,2; Christiane Peters1;
Renate Oberhoer-Fritz1; Irene von Lüttichau2
1Institute of Preventive Pediatrics, Department of Sport and Health Sciences,
Technical University of Munich, München, Deutschland
2Kinderklinik München Schwabing, TUM School of Medicine, Department
of Pediatrics and Children’s Cancer Research Center, Technical University of
Munich, München, Deutschland
Purpose: Treatment of childhood cancer is associated with physical inac-
tivity, a reduced quality of life and motor performance. erefore, sports
interventions over all phases of treatment might be a supportive therapy
option to improve the patients’ physical and mental well-being.1
Methods: e approach of accompanying sports therapy was implement-
ed by a feasibility study at our department. Aiming at a holistic model
we promote physical activity from diagnosis to aercare during in- and
outpatient treatment among children from 2 years. Accomplishing the ob-
jectives sport scientists work closely together in an interdisciplinary team.
Furthermore, continuity is ensured supporting the process of reintegra-
tion into sports structures among childhood cancer survivors.
Results: Since sports therapy was established in June 2016, 177 patients
(9.0±4.5 yrs, 62% ♂) with dierent cancer entities participated in a daily
sports program. Two part-time sports scientists provided 1776 exercise
sessions (57.5% inpatient) with mean duration of 28.4±15.9min. Train-
ing content and intensity were specically adjusted regarding age, inter-
ests and individual exercise capacity. Various sports groups and outdoor
camps are completing our oers in the aercare.2
Conclusions: Continuous sports promotion over all phases of treatment
increases physical activity and supports the maintenance of mobility and
autonomy. In order to develop a long-term active lifestyle and reduce pos-
sible disease- and therapy-related late eects the patients have to be sus-
tainable encouraged aer diagnosis. Further multi-center research proj-
ects will be essential to investigate the eects of physical exercise during
pediatric cancer treatment with the intension of establishing sports thera-
py as part of standard care.
References:
1. Braam KI et al. (2016). Physical exercise training interventions for children
and young adults during and aer treatment for childhood cancer. Cochrane
Database Syst Rev.
2. Abstracts from the 51st Congress of the SIOP Lyon, 2019. Pediatric blood &
cancer 66 Suppl 4, e27989.
1048
T Cell Receptor Based Immunotherapy in Immune Inert
Pediatric Malignancy: Addressing the Challenge of Early
Metastasis and Low Immunogenicity
Stefan Burdach1; Günther Richter1; David Schirmer1; Andreas Kirschner1;
Sebastian Schober1; Valentina Evdokimova2; Hendrik Gassmann1; Elvira
D‘ippolito3; Maxim Barenboim1; Dirk Busch3; Poul Sorensen4; Uwe Thiel1
1Department of Pediatrics and Children‘s Cancer Research Center, Kinderklinik
München Schwabing, Technical University of Munich School of Medicine,
München, Deutschland
2Ontario Institute for Cancer Research, Toronto, ON, Canada.
3Institute of Medical Microbiology, Immunology and Hygiene, Technical
University of Munich School of Medicine, München, Deutschland
4Department of Molecular Oncology, BC Cancer Research Centre, Vancouver,
BC, Canada.
P:Most pediatric malignancies, in particular Ewing sarcoma (EwS) are
characterized by low mutational load, low immunogenicity, and early me-
tastasis. Ideally, targeted therapies address gene products required for me-
tastasis. We completed in vivo functional analyses for metastasis of 9/37
genes that we had shown to be overexpressed in EwS (Staege at al.Cancer
Res. 2004) and generated HLA class I restricted cytotoxic T cells against
these gene products.
M:All targets were involved in fetal development and 8/9 demonstrated
functional relevance for metastasis. Allorecognition repertoire-derived
T Cell Receptors (TCRs) against 8/9 targets were cloned and sequenced;
one target (DKK2) was non-immunogenic. 7/8 TCRs were cross reac-
tive, caused fratricide or clonal TCR expansion failed. In the tumor mi-
croenvironment we found an immunosuppressive transcriptomic signa-
ture.Amongst these most selectively expressed and metastasis sustaining
targets, chondromodulin-I (CHM1) was addressable by a non-cross re-
active TCR. CHM1 is a direct downstream target of the oncogenic driver
EWS-FLI1.
We clinically assessed HLAA* 02:01/CHM1-specic TCR transgenic
CD8+T cells against EwS. Four refractory HLA-A2+ EwS patients (pts)
were treated with CHM1319-specic TCR-CDR3 transgenic T cells. Pt de-
rived cell lines (PDCL) were established in all cases. Pts received up to
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107/kg TCR transgenic CD8+ T cells. All pts were treated with the same
TCR-CDR3 recognition-sequence for CHM1.
R: All PDCLs displayed persistent HLA-A2 expression. Transgenic T cells
showed specicin vitrolysis of all PDCLs. Pt #1 #3 and #4 showed delayed
progression, whereas pt #2, while having bone marrow (BM) involvement
and accessible multifocal disease, showed partial metastatic regression as-
sociated with T cell homing to involved lesions.
C: CHM1319-TCR transgenic T cells may home to aected BM & may
cause partial remission. CHM1-TCR transgenic T cells address a per-
sistently expressed target required for metastasis, suggesting lack of im-
munoediting selection pressure. ey proliferatein vivowithout causing
GvHD.
Palliative Care
Poster
1051
Symptom Burden of Cancer Patients Ad Admission to a
Palliative Care Unit: Cancer-Related Fatigue is Predominant
Parvis Sadjadian; Tatjana Becker; Kai Wille; Martin Griesshammer
Johannes Wesling Klinikum Minden, Ruhr-Universität Bochum,
Universitätsklinik für Hämatologie, Onkologie, Hämostaseologie und
Palliativmedizin, Minden, Deutschland
Introduction: Cancer-related fatigue (CRF) is frequent in advanced stage
cancer patients with an enormous impact on quality of life. In this survey
we investigated the symptom burden of in-patient palliative care patients
at the time of admission to our palliative care unit focussing on CRF.
Methods: Starting July 1st 2019, we questioned all cancer patients (pts.)
during the admission process to our palliative care unit about the 3 most
troublesome symptoms. Besides demographic data, we captured tumor
type, ECOG performance status (PS) and application of any tumor thera-
py (chemotherapy, antibody or targeted therapy, radiotherapy) in the last
6 month prior to admission. A special interest was set on the existence
and severity of CRF using the brief fatigue inventory (BFI), available and
validated in german language.
Results: 105 tumor patients (51 women, 54 men, median age 70.8 years,
mean ECOG PS 3.5) with 26 dierent malignancies were eligible. e 3
most frequent tumor types were lung cancer (23 pts., 21.9%), breast cancer
(11 pts., 11.5%) and pancreatic cancer (13 pts., 12.4%). e most frequent-
ly reported tumor symptoms were fatigue (78%), pain (54%), cachexia/
anorexia (39%), psychologic symptoms (29%), dyspnea (22%), neurologic
symptoms (22%), nausea/vomiting (17%) and constipation (10%). 73 pa-
tients (69.5%) were able and willing to complete the BFI, mean BFI Score
was 6.4. 7 pts. (9.5%) had mild fatigue (BFI score < 4), 35 pts. (47.9) had
moderate (BFI score ≥ 4 and < 7) and 31 pts. (42.5%) had severe fatigue
(BFI Score > 7). Fatigue was most prevalent in breast cancer pts. (91%,
mean BFI score 6.3), similarly high in patients with lung (78%, mean BFI
score 6.7) and pancreatic cancer (75%, mean BFI score 5.4).
34.9% of the patients received any tumor therapy in the last 6 weeks prior
to admission. 82.8% of those pts. reported fatigue with a mean BFI score
of 7.0, comparing to 70.4% and a mean BFI score of 6.4 in the 65.1% of pts.
with no recent tumor therapy.
Conclusions: CRF is by far the predominant symptom of cancer patients
and mostly the main cause for admission to our palliative care unit.
Psychooncology
Poster
921
Development and Validation of the Readiness for End-of-Life
Conversations (REOLC) Scale
Pia Berlin; Nico Leppin; Katharina Nagelschmidt; Winfried Rief;
Pia von Blanckenburg
Klinische Psychologie und Psychotherapie, Philipps-Universität Marburg,
Marburg,
Purpose: Being treated with respect and asked for wishes at the end of
life (EOL) is oen dened as key factor of a “good death. However, peo-
ple tend to avoid preparations for death until they are unexpectedly con-
fronted. en stress, anxiety, isolation and depression are experienced
and wishes not known. In order to reduce barriers of preparedness and
provide interventions to further increase readiness, people in dierent
stages of readiness need to be identied and intervention eects need to
be measured correctly. e present study focused on development and
validation of a questionnaire to assess peoples’ readiness to engage in EOL
conversations [1].
Methods: irteen Items that have been answered by a healthy control
sample (N = 213) were analyzed using exploratory factor analysis. Items
were excluded based on insucient contributions to factor loadings, in-
ternal consistency and theoretical value to the scale.
Results: Two factors were extracted. Readiness (8 items) explained 73%
of variance with factor loadings ranging from λ1 = 0.50 – 0.80 (Cronbachs
α = .87). Acknowledgment of values (3 items) explained 27% of variance
with factor loadings ranging from λ2 = 0.53 – 0.76 (Cronbachs α = .61).
Conclusions: Preliminary results indicate that readiness to engage in
discussion about EOL and assessment of values explain healthy peoples
readiness and can be used to identify the extent of readiness and changes
aer interventions. As a next step the questionnaire is currently validated
in a sample of cancer patients.
Reference:
1. Abba, Katharine; Byrne, Paula; Horton, Siobhan; Lloyd-Williams, Mari (2013):
Interventions to encourage discussion of end-of-life preferences between mem-
bers of the general population and the people closest to them - a systematic
literature review. In: BMC palliative care 12 (1), S. 40. DOI: 10.1186/1472-
684X-12-40.
Disclosure Statement: In preparation
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970
Fostering Communicative Competence and Performance of
Physicians (KPAP Study Protocol) – Multimodal Assessment of
Long Term Eects of a Communication Trainings Programme
(Funded by German Cancer Aid)
Frank Vitinius1; Stephanie Stock2; Alexander Wünsch3; Martin Hellmich4;
Helena Langewitz5; Hannah Fischer1; Michaela Henning1; Wolfgang
Söllner6; Barbara Stein6
1Klinik und Poliklinik für Psychosomatik und Psychotherapie, Uniklinik Köln,
Köln,
2Institut für Gesundheitsökonomie und Klinische Epidemiologie (IGKE),
Uniklinik Köln
3Tumorzentrum Freiburg - CCCF Psychosoziale Krebsberatungsstelle Freiburg, in
Kooperation mit der Klinik für Psychosomatische Medizin und Psychotherapie,
Uniklinik Freiburg
4Institut für Medizinische Statistik und Bioinformatik (IMSB), Uniklinik Köln
5Kommunikation in der Medizin, Basel, Schweiz, Unispital Basel
6Klinikum Nürnberg, Klinik für Psychosomatische Medizin und Psychotherapie,
PARACELSUS Medizinische Privatuniversität
Purpose: Communication trainings improve communication skills of
health care professionals in oncology. Only sparse data exists regarding
long-term eects of communication trainings for physicians. e aim of
this project is to investigate in a multimodal approach self-assessment of
the physicians and external assessment of these physicians by experts and
trained patient raters three years aer a communication skills training
(CST).
Methods: Until now, nearly 170 physicians have participated in the train-
ing program “Kommunikative Kompetenz” of the University Hospital of
Cologne based on the KoMPASS project. Self-reported questionnaires
(empathy, burnout, self-condence etc) are lled in at baseline and at the
end of the 2.5 days CST (t0 and t1), at the 6 hours refresher session at least
three months later (t2) and, as part of the funded study, at least three years
later (t3).
Delivering bad news with standardized simulation patients and partici-
pants were videotaped at t0 and t2 and in a subsample (n=60) at t3. Patient
raters and expert raters will assess the videos using the AGBS as primary
outcome (breaking bad news) and the ComOnRating Scale (communica-
tion skills in oncology). Experts will assess these videos regarding RIAS,
patients by using the perceived empathy scale CARE.
Results: e study protocol will be presented.
Conclusions: is multimodal assessment may allow to proof the sustain-
ability of the CST program and to detect dierences and similarities of the
three assessment perspectives.
Reference:
1. Vitinius F ….. Keller M. [KoMPASS--design, implementation and experiences
concerning a structured communication skills training for physicians dealing
with oncology]. PPmP 2013
Disclosure Statement: Funding by DFG, BMBF, Innovationsfonds and DKH, fees
for CSTs.
974
Anxiety and Depression Predict Decisional Conict in Shared
Decision Making
Anja Kristina Köther1; Georg W. Alpers1; Björn Büdenbender1;
Maximilian Lenhart2; Maurice S. Michel2; Maximilian C. Kriegmair2
1Chair of Clinical and Biological Psychology and Psychotherapy, School of Social
Sciences, University of Mannheim, Mannheim, Deutschland
2Medical Faculty Mannheim, Heidelberg University, Mannheim, Deutschland
Purpose: Receiving or anticipating a serious diagnosis like cancer can be
a profound experience and oen results in negative emotional respons-
es. Such negative aect may inuence how conicted patients feel about
treatment choices. is poses a potential barrier to shared decision mak-
ing (SDM). Yet, aect is typically not systematically assessed in medical
consultation. us, we examined whether patients report anxiety and
depression prior to a urological consultation and if emotional distress
predicts decisional conict aer SDM.
Methods: We recruited a large sample of urological out-patients (N = 227)
with a range of dierent diagnoses (40% uro-oncological) at a university
hospital. Prior to a medical consultation, patients lled in a set of vali-
dated questionnaires including socio-demographic characteristics and the
Hospital Anxiety and Depression Scale. Aer the consultation, patients
completed the Decisional Conict Scale. We calculated the prevalence of
anxiety and depression in our sample and conducted regression analysis
to examine if emotional distress before the consultation predicts decision-
al conict aer.
Results: Overall, there was a broad range of anxiety and depression scores,
with 24% of patients reaching values at or above cut-o for clinically rel-
evant emotional distress. ere were no signicant dierences in emo-
tional distress between patients with an oncological and non-oncological
diagnosis. Although only few patients reported high levels of decisional
conict, emotional distress signicantly predicted a higher degree of deci-
sional conict which accounted for 10% of variance.
Conclusions: Negative emotions were oen reported prior to clinical de-
cision-making in urological patients, independent of diagnosis. Most im-
portantly, anxiety and depression predicted more decisional conict aer
a medical consultation. us, emotional distress should be systematically
assessed and addressed in clinical consultations to improve the outcome
of SDM and to help identify patients who may benet from additional
support.
1006
Patients’ Attitudes and Beliefs can be a Barrier to Shared
Decision Making
Björn Büdenbender1; Anja K Köther1; Maximilian Lenhart2;
Maximilian C Kriegmair2; Maurice Stephan Michel2; Georg W Alpers1
1Lehrstuhl für Klinische und Biologische Psychologie und Psychotherapie,
Universität Mannheim, Mannheim, Deutschland
2Klinik für Urologie und Urochirurgie, Universitätsklinikum Mannheim,
Mannheim, Deutschland
Purpose: In oncology, patients are confronted with complex treat-
ment-decisions. Discrete treatment options may be equally eective and
supported by medical evidence while they may dier in their impact on a
specic patients life. erefore, options are ideally selected with active in-
volvement of the patient; a process called shared decision making (SDM).
While many structural aspects are known to inuence whether SDM is
put into practice, a patients individual characteristics may also be rele-
vant. e primary goal of this study is, to investigate the eect of patients
attitudes and beliefs on their willingness to take a more active role.
Methods: e Patients’ Attitudes and Beliefs Scale (PABS) was trans-
lated and backtranslated independently. We recruited a patient sample
(N = 225) at a university hospital, as part of an ongoing study. Patients
were between 19 and 85 years old and had a wide range of diagnoses
(43.6% uro-oncological). In addition to the PABS-D, patients’ preference
for participation was assessed with the Autonomy Preference Index (API).
Preliminary analyses were based on multiple linear regression.
Results: First, we replicated the association of participation preference
and sociodemographic factors. Second, Patients’ positive and negative at-
titudes were a strong predictor of their participation preference and their
intention to participate in the decision. ird, when we control for these
attitudes and beliefs, the inuence of sociodemographic factors is reduced.
Lastly, psychometric properties of the translated PABS-D are promising.
Conclusions: Negative attitudes and beliefs limit patients in their inten-
tion to participate in SDM independent of the well-established inuence
of sociodemographic factors. Importantly, in contrast to sociodemo-
graphic factors, attitudes and beliefs may be targets for interventions such
as supplying patients with individualized information. us, future eorts
to implement SDM may benet from systematically assessing attitudes
and beliefs.
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Radiation
Poster
1050
Development of Admission to Radiotherapy Departments in
Germany: A Population-Based Study of DRG Data
Daniel Medenwald1; Susan Langer1; Andre Glowka1;
Katharina Medenwald1; Dirk Vordermark1
1Martin-Luther-Universität Halle-Wittenberg, Klinik für Strahlentherapie, Halle
(Saale), Deutschland
Purpose: With the increasing complexity of oncological therapy, the
amount of inpatient admission to radiotherapy departments might have
changed. In this study, we aim to quantify the proportion of inpatients
receiving radiotherapy in radiation oncology units and respective devel-
opments since 2008.
Method: e analysis is founded on data of all hospitalized cases in Ger-
many based on Diagnosis-Related Group Statistics (G-DRG Statistics, de-
livered by the Research Data Centres of the Federal Statistical Oce and
the Statistical Oces of the federal states1).
e data set includes information on the main diagnosis and the proce-
dures that were performed during the hospitalization and are relevant for
claims of reimbursement. We used linear regression models to analyse
temporal trends.
e considered data encompass the period from 2008 to 2014 and are
presented in a monthly pattern (smallest available time unit).
Results: Starting in 2008, 48.9% of a cases received their treatment sole-
ly in a radiation oncology unit. is gure decreased to 45.0% in 2014.
We found a steplike decrease between December 2011 and January 2012
amounting to 4.3% (absolute case numbers of 685.3; 95% CI: 480.0-890.6).
For cases not treated in radiotherapy departments numbers remained vir-
tually constant. Fractions received in radiotherapy departments decreased
slightly by 34.4 (95% CI: 12.4-56.3) fraction per month. e total duration
spent in radiotherapy units decreased by 76.5 (95% CI: 41.9-111.0) days
per month starting from a total of 64,842 days in January 2005 to 45,003
days in 2014.
Conclusion: Our data give evidence to the notion that radiotherapy re-
mains a discipline with an important inpatient component. As treatment
become more complex and patients become older, radiotherapy clinics
could sustain a steady number of case numbers.
Reference:
1. www.forschungsdatenzentrum.de
Disclosure Statement: ere is no conict of interest
Rehabilitation and Long-term Burden in Social Medicine (Survivors)
Poster
969
Potency After Nervesparing Prostatectomy and Results
4 Years Postoperatively, a Retrospective Comparison of
Three Surgical Methods
Anika Biel
Abteilung Urologie, Müritzklinik Klink, Klink
Purpose: Radical prostatectomy is a standard procedure for the treatment
of prostate cancer. e surgery can be performed dierently, established
are open, laparoscopic and robotic surgical procedures. It is increasingly
trying to perform the operation nerve sparing. is can be done on one
side or on both sides. e aim is to record with which OP method a nerve
sparing is most oen to achieve and to determine the rate of spontaneous
erections postoperatively.
Methods: In May 2019, a standardized written survey of the patients who
had a rehabilitation aer radical prostatectomyctomy or aer curative ra-
diation in the period 2015-2016in the Müritz-Klinik. e patients were
interviewed regarding a nerve-sparing surgical procedure, the possibility
of getting a sucient erection for sexual intercourse, and the remedies
that may be used.
Results: From 716 patients, 409 patients responded, 337 of whom were op-
erated in 2015. is corresponds to a rate of 82.40%. 152 patients (45.10%)
used nerve sparing procedures. Particularly oen, the robot-assisted sur-
geries were nerve-sparing (71.19%) and the laparoscope. (37.70%) and the
open (40.09%) surgeries were signicantly less. Averaged over all three
surgical methods, 23.68% of the nervously operated reported to be able to
have sexual intercourse again without any aids. Broken down, this can sig-
nicantly more lap. (30.43%) and roboterass. (28.57%) as open operated
(19.54). e most commonly used adjuncts are the use of PDE-5 inhibi-
tors and the penis pump.
Conclusions: Sexuality is an important factor in human quality of life. As
early as 2015, 45.10% of surgeries were carried out nervesparing. Only a
little more than every 5th patient gets a sucient erection for sexual in-
tercourse, despite the fact that the nerve is protected. Minimally invasive
surgical techniques are an advantage here. In the course of optimizing the
surgical methods seems to further improve the postop. erectile function
possible.
Disclosure Statement: No
1010
Relationship between Nerve-Sparing Prostatectomy and
Continence a Retrospective Survey
Anika Biel
Urologie, Müritz-Klinik, Klink, Deutschland
Purpose: Radical prostatectomy is a standard procedure for the treatment
of prostate cancer. e operation can be carried out in dierent ways,
open, laparoscopic and robotic surgical procedures have been established.
Attempts are increasingly being made to carry out the operation in a
manner that is to preserve the dorsolateral vascular nerve bundle. is
can be done on one or both sides. A connection between continence and
nerve-sparing is reported. e aim of our survey was to nd out whether
the eect would continue for four years postoperatively.
Methods: ere was a standardized written survey in May 2019 of pa-
tients who received inpatient rehabilitation at the Müritz Clinic aer rad-
ical prostatoviculectomy or aer curative radiation in the period 2015-
2016. e survey was carried out with regard to a nerve-holding operation
and the current continence status.
Results: Out of 716 letters, 409 responded. 337 of these were operated on
in 2015, which corresponds to a rate of 82.40%. In 152 patients (45.10%)
nerve-sparing procedures were used. Especially oen the robotic opera-
tions are nerve-saving (71.19%), lap (37.70%) and open (40.09%) opera-
tios were signicantly less.
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With all surgical methods it can be seen that patients with nerve spar-
ing are four years postoperatively more continent (60.53%) than patients
without (45.41%). Broken down according to the surgical methods, the
following constellation shows that 47.48% of the openly operated patients
with nerve-sparng are continent. 44.62% without. In laparoscopic pros-
tatectomised patients with nerve-sparing, 60.87% are continent, without
nerve-sparing 42.11%. Among the robotically operated, 66.67% are conti-
nent with nerve-sparing, 58.82% without.
Conclusions: Long-term observation shows a positive eect of
nerve-sparing surgery on continence. is is particularly pronounced in
our lap patient population. In contrast, the dierence is not signicant for
open surgery.
Sarcoma
Poster
990
Ewing Sarcoma of the Kidney in a 23-Year Old Female: An
Interdisciplinary Workup of an Uncommon Entity
Nalyan Ali; Susan Foller; Marc-Oliver Grimm
Universitätsklinikum Jena, Klinik und Poliklinik für Urologie, Jena, Deutschland
Purpose: Ewing sarcoma predominantly occurs in the bones such as
pelvis, femur, humerus but, however, it can occur anywhere in the body.
It usually aects teenagers and younger adults. Primary Ewing sarcoma
of the kidney is a rare type of malignant tumor and its preoperative dis-
crimination from benign renal masses as well as renal cell carcinomas is
dicult.
Methods: We present a case of a 23-year-old woman with pre-, intra- and
postoperative imaging and review the literature for this kind of malig-
nancy.
Results: Our female patient presented with unspecic symptoms such as
generally feeling unwell and fatigue over a period of 4 months. Physical
examination, urinalysis and serum biochemistry via general physician
remained without pathological ndings. An ultrasound of the abdomen
showed a suspicious mass of the le kidney measuring 4 x 4 cm. Subse-
quent evaluation with MRI conrmed a solid tumor at the lower pole of
the le kidney which appeared malignant. erefore, a partial nephrec-
tomy through a lumbar incision was performed. e treatment was well
tolerated and no relevant complications occurred. Histopathological ex-
amination revealed an extra osseous Ewing sarcoma of the kidney (pT1,
L0, V0, Pn0, G3, R0). FDG-PET-CT and cerebral MRI ruled out distant
metastases (cN0, cM0). Adjuvant multidrug chemotherapy (6 courses
VIDE (vincristine, ifosfamide, doxorubicin, etoposide) and a close fol-
low-up was recommended by the multidisciplinary tumorboard. Before
chemotherapy started patient went for oocytes cryopreservation.
Conclusions: is case demonstrates that even patients with non-spe-
cic symptoms should undergo careful physical examination including
imaging e. g. ultrasound. However, tumor entity oen remains unclear
despite imaging and surgery is required even in younger patients. Rare
malignancies as primary Ewing sarcoma of the kidney require close in-
terdisciplinary cooperation between urologists, radiologists, oncologists
and pathologists.
Skin Cancer, including Melanoma
Poster
1038
Variant Eects of Ingenol Mebutate on Apoptosis Regulation
in Cutaneous T-Cell Lymphoma Cells
Uly Sumarni; Ulrich Reidel; Jürgen Eberle
Charité – Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und
Allergologie, Berlin, Deutschland
Purpose: Ingenol mebutate (PEP005, Picato®) has been described to dis-
play proapoptotic activity in neoplastic lymphocytes in vitro. While a clin-
ical study suggested that topical treatment may be benecial for CTCL
patients (Ref 1), its mode of action remained elusive. For apoptosis reg-
ulation in CTCL cells, the extrinsic caspase cascade and reactive oxygen
species (ROS) are of particular importance (Ref 2). Here, the eects of
ingenol mebutate were investigated in CTCL cell lines.
Methods: CTCL cell lines: HH, HuT-78, MyLa and SeAx. Apoptosis: cell
cycle analysis aer propidium iodide staining; cell viability: calcein stain-
ing and ow cytometry; cell proliferation: WST-1 assay. Mitochondrial
membrane potential and ROS: ow cytometry aer staining with TMRM+
and H2DCF-DA, respectively. Western blotting for caspase-3, caspase-8
and cFLIP (Flice-inhibitory protein).
Results: CTCL cell lines revealed highly dierent responses to ingenol
mebutate. While HuT-78 and HH showed high and moderate sensitivi-
ty, respectively, MyLa and SeAx appeared as resistant. Ingenol mebutate
resulted in loss of mitochondrial membrane potential in HuT-78 as well
as in enhanced ROS in HH and HUT-78. Inhibition of ROS in HH by
the antioxidant α-tocopherol resulted in suppressed apoptosis. Finally,
proapoptotic caspases 3 and 8 were activated in HH and HuT-78, as well
as c-FLIP was downregulated in HH. e apoptosis inhibitor c-FLIP was
also stronger expressed in resistant cell lines MyLa and SeAx.
Conclusions: Ingenol mebutate may be considered as strategy for treat-
ment of some CTCL patients, while others may not prot from this ther-
apy. us, reliable markers for responsiveness are needed. Its mode of
action in CTCL cells is related to caspase activation and ROS production.
References:
1. Lebas E, Castronovo C, Arrese JE, Libon F, Tassoudji N, Seidel L, Nikkels AF
(2017) e Open Dermatology Journal 11: 98-107.
2. Soltan MY, Sumarni U, Assaf C, Langer P, Reidel U, Eberle J (2019) Int J Mol
Sci 20: E1158.
Disclosure Statement: No conict of interest
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2018
Index
2018
1039
Microrna-Mediated MCL-1 Silencing in Melanoma Cells
Enhances the Pro-Apoptotic Potential of BRAF and ERK 1/2
Pathway Inhibitors
Zina Sarif; Aybige Dogan; Jürgen Eberle
Department of Dermatology, Venerology and Allergology, Skin Cancer Center
Charité, Charité-Universitätsmedizin Berlin, Berlin, Deutschland
Purpose: BRAF and MEK Inhibitors have revolutionized standard care
of melanoma patients. However, despite clear clinical benets, emergence
of drug resistance is limiting their success. Mcl-1 is a potent antiapoptotic
protein and highly amplied in human cancer including melanoma. Cur-
rent data showed that extensive expression of Mcl-1 in melanoma is asso-
ciated with tumor progression, and resistance to BRAF inhibition. Aim of
this study is to assess the eects of Mcl-1 inhibition in combination with
BRAF and ERK inhibitors.
Methods: Mcl-1 was inhibited via miR-193b-3p and miR-339-3p as well
as by the selective inhibitor S63845. Mcl-1 expression, ERK and caspase
activation was dened by Western blot analysis. Cell viability, apoptosis
induction, mitochondrial membrane potential as well as Bax and Bak ac-
tivation were determined by ow cytometry, cell proliferation by WST-1
assay.
Results: We show high eciency of the BRAF inhibitor Vemurafenib in
combination with the Mcl-1 inhibitor S63845, driving a high apoptosis
via Bax and/or Bak activation. Furthermore, we develop miRNA-based
strategies for Mcl-1 targeting using miR-193b-3p and miR-339-3p. Com-
parable to Mcl-1 inhibitor, miR-193-3p in combination with Vemurafenib
resulted in strong apoptosis induction (up to 80%). Also, the combina-
tion of S63845 with the ERK inhibitor SCH772984 strongly enhances the
proapoptotic ecacy in BRAF-wt melanoma cells.
Conclusions: Targeting Mcl-1 in combination with MAPK pathway in-
hibitors in melanoma could improve the therapeutic index and patient´s
outcomes. In addition to pharmacological inhibition, miR-193b-3p might
represent a useful genetic approach for ecient Mcl-1 targeting.
References:
1. Franklin C, Livingstone E, Roesch A, Schilling B, Schadendorf D (2017) Jour-
nal of the European Society of Surgical Oncology and the British Association
of Surgical Oncology 43:604-611
2. Beroukhim R, Mermel CH, Porter D, et al. (2010) Nature 463:899-905
Disclosure Statement: No conict of interest
1045
Mutual Enhancement of Apoptosis in Cell Lines of Cutaneous
Squamous Cell Carcinoma by Combination of Celecoxib and
Death Ligands
Jiaqi Zhu1,2; Stefanie May1; Claas Ulrich1; Eggert Stocketh3; Jürgen Eberle1
1Charité – Universitätsmedizin Berlin , Klinik für Dermatologie, Venerologie und
Allergologie, Berlin, Deutschland
2Jilin University, Department of Gynecology and Obstetrics, Changchun, China
3Ruhr-Universität Bochum, Katholisches Klinikum Bochum, Dermatologie,
Venerologie und Allergologie, Bochum, Deutschland
Purpose: Actinic keratosis (AK) shows strongly increasing prevalence
in fair-skinned populations worldwide and may proceed into cutaneous
squamous cell carcinoma (cSCC). Important risk factors are UV irradi-
ation and immunosuppression. Nonsteroidal anti-inammatory drugs
(NSAIDs), as diclofenac and celecoxib, are considered and are partly ap-
proved for treatment. While synergistic eects of celecoxib and immune
modulators as anti-PD1 or anti-PDL1 have not been reported so far, this
seems to play role in the mode of action of other NSAIDs.
Methods: Cutaneous SCC cell lines: SCL-I, SCL-II. SCC-12, SCC-13.
Apoptosis: cell cycle analysis aer propidium iodide staining; cell viabil-
ity: calcein staining and ow cytometry; cell proliferation: WST-1 assay.
Mitochondrial membrane potential and ROS: ow cytometry aer stain-
ing with TMRM+ and H2DCF-DA, respectively.
Results: Celecoxib resulted in signicant, dose-dependent antiprolifera-
tive eects in four cSCC cell lines, accompanied by strongly enhanced in-
tracellular ROS levels. However, moderate concentrations (25 µM, 50 µM)
did not eciently aect apoptosis or cell viability, which are fundamental
for anticancer treatment. As highly eective appeared the combination
of celecoxib with death ligands (CD95/Fas ligand, TRAIL), which result-
ed in up to 60% apoptosis and almost complete loss of cell viability. is
was accompanied by loss of mitochondrial membrane potential. Western
blotting revealed downregulation of the antiapoptotic Bcl-2 protein Mcl-1
and of the caspase-3 antagonist XIAP (chromosome X-linked inhibitor of
apoptosis protein).
Conclusions: As CD95L and TRAIL are also produced by the immune
system, these ndings suggest that celecoxib can enhance the antitumor
eects of the immune system is may also explain the eciency of com-
binations with checkpoint inhibitors (anti-PD1), recently approved for
treatment of cSCC.
Disclosure Statement: No conict of interest.
Supportive Care
Poster
45
Benets from Exercise Training in Pediatric Oncology: Results
from the Randomized Controlled Mucki-Trial
Sandra Stössel1; Marie Astrid Neu1; Arthur Wingerter1; Wilhelm Bloch2;
Philipp Zimmer2,3; Claudia Paret1; Khalifa El Malki1; Freerk T. Baumann4;
Nicole Henninger1; Alexandra Russo1; Nadine Lehmann1; Henrike Otto1;
Joerg Faber1
1Childhood Cancer Centre, University Medical Centre Mainz- Centre for Pediatric
and Adolescent Medicine, Mainz, Deutschland
2Institute of Cardiovascular Research and Sports Medicine, German Sport
University Cologne, Köln, Deutschland
3Department for physical activity, preventive research and cancer, German
Cancer Research Center, Heidelberg, Deutschland
4Department I of Internal Medicine- Center of Integrated Oncology , University
Hospital of Cologne, Köln, Deutschland
Purpose: Disease- and treatment-related reductions of muscular and
aerobic performance have been observed in childhood cancer patients.
In adult cancer patients, specic exercise training revealed positive eects
on muscular and aerobic capacity which were associated with benets on
fatigue and quality of life. Within the “Eects of Combined Resistance
and Endurance Training in Pediatric Cancer Patients During Intensive
Treatment Phase (MUCKI)-trial” training eects on muscular and walk-
ing performance were evaluated.
Methods: In this stratied randomized controlled trial, childhood can-
cer patients aged between 4 and 18 years were enrolled during intensive
cancer treatment phase (ICT). Individuals within the exercise group (EG)
participated in supervised exercise training. Training was focused on child
adapted playful, moderate intense resistance and endurance exercises and
took place 3 to 5 times weekly over a period of 6 to 8 weeks. Individuals
of the control group (CG) received usual care. Pre- and post-interven-
tion handheld dynamometry testing for knee exor strength and six min-
ute-walk test were performed.
Results: In total 16 patients in the EG and 17 in the CG completed the
study. Group-time-interactions on muscular and walking performance
were evaluated by analysis of covariance adjusting for baseline values and
stratication factors. Subsequent results revealed favoring eects for EG in
knee exor strength (F(1,20)=5.733; p=0.027; η2p=0.223) and walking
performance (F(1,25)=4.270; p=0.049; η2p=0.146). Compliance to the
training was rated very good to good, no severe adverse events occurred.
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Conclusions: e present results provide further evidence for benecial
eects from adapted exercise programs in childhood cancer patients suf-
fering from dierent tumor entities. Adapted pediatric exercise programs
are getting attention only recently. In this context, the present ndings
support further elaboration and implementation of adapted exercise oers
in pediatric oncology.
Abstract also submitted 2019: SIOP, EIM, UCT Sc. Day Mainz, DVS
960
Pilot Case-Series: Can Short-Term WBEMS be Eective in
Cancer Patients?
Timo Niels1; Jane Kersten2; Annika Tomanek1; Freerk Baumann1
1Klinik I für Innere Medizin, Universitätsklinikum Köln, Köln, Deutschland
2Deutsche Sporthochschule Köln, Köln, Deutschland
Purpose: e loss of body weight, muscle mass and function is a severe
but common burden in cancer patients. Innovative exercise methods, such
as whole-body electromyostimulation (WB-EMS) seem to be a potent
and safe alternative to conventional exercise types to maintain or improve
body mass and function. Due to its time-saving nature and low-thresh-
old even for non-exercising patients, the question arises if WB-EMS also
could be applied eectively in a short duration such as two weeks.
Methods: is pilot case-series included 13 cancer patients with diverse
entities, disease stages and phases of treatment, which were exercised with
supervised WB-EMS four times within two weeks. Physical functioning
and self-reported outcomes as quality of life, fatigue and depression were
assessed before and aer the exercise period. Also, the patient’s subjective
body perception was documented prior and post every exercise session.
Results: All 13 patients were able to perform the four WB-EMS sessions.
No adverse events occurred. Within the descriptive statistics, the patients
showed improved muscle strength and maintained or improved their car-
diovascular performance. WB-EMS exercise also seems to be benecial
in depression and anxiety scores and global quality of life. Nevertheless,
the exercise showed some negative impacts on the patients fatigue and
some symptom domains, such as diarrhea or overall pain. e patient’s
subjective body perception following a WB-EMS session was increased in
all four sessions and additionally showed reductions in domains of tem-
porarily pain and discomfort.
Conclusions: WB-EMS seems to be a safe and feasible exercise meth-
od for cancer patients. Although exercise duration was relatively short,
the ndings suggest a positive impact on physical performance and
patient-reported outcomes, indicating a potential use of WB-EMS in short
time-frames, such as pre-surgery or pre-chemotherapy. However, this
exercise method seems to be at risk of exacerbating the patient’s fatigue,
what should be monitored with caution and addressed in future trials.
984
Using a New Controlled Thermotherapy (Hilotherapy®)
During Chemotherapy Prevents Chemotherapy Induced
Polyneuropathy
Trudi Schaper1,,2; Mahdi Rezai3; Maren Darsow4
1Luisenkrankenhaus GmbH & Co KG, Studienzentrale, Düsseldorf, Deutschland
2Internationale Senologie Initiative ISI e.V, Selbsthilfe, Düsseldorf,
3Praxis Dr. Rezai, Senologie, Düsseldorf,
4Luisenkrankenhaus GmbH & Co KG, Brustzentrum, Düsseldorf, Deutschland
Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is
an adverse eect of many commonly used chemotherapeutic agents, espe-
cially taxane-based regimen (Paclitaxel, nab-Paclitaxel, Docetaxel). CIPN
reduces patients health-related quality of life for years and oen results in
dose delay, dose reduction or treatment discontinuation. e prophylactic
use of controlled thermotherapy (Hilotherapy®) prevents CIPN.
Method: 172 breast cancer patients used the prophylactic Hilotherapy®,
a new method of physical thermotherapy device, equiped with hand and
foot cus to allow a constant cooling.
Continous cooling of hands and feet was performed 30 minutes before to
60 minutes aer completing drug infusion with a temperature of 10-12°C.
CIPN symptoms were evaluated aer each cytotoxic cycle using common
terminology criteria for adverse events (CTCAE).
Sustainability of the impact was assessed by long-term datas (every
3 months).
130 patients used the prophylactic Hilotherapy® for each cytotoxic treat-
ment (Group 1: primary Prophylactic Hilotherapy® - pPHT).
Results: From 130 patients using pPHT, 121 patients (93%) developed
none or mild symptoms of CIPN (grade 0-1). 8 patients (6,1%) reported
grade 2, 1 patient grade 3 (0,8%) toxicity.
e symptoms of CIPN were reversible. 4 months aer chemotherapy,
98% of the patients had no CIPN > grade 1, 2 patients (2%) suered inter-
mittent toxicity grade 2.
Without using pPHT 50% of the patients developed grade 3 and 2 CIPN.
e sustainability of the impact was assessed by long-term datas (Follow
Up patient contact every 3 months).
Conclusions: Prophylactic Hilotherapy prevented limiting CIPN Symp-
toms (> grade 1) in 93% of patients. 4 months aer chemotherapy treat-
ment, 98% of the patients were without any limiting symptoms (grade ≤ 1).
No dose modications or treatment interruptions had been necessary.
Without pPHT 50 % of the patients developed CIPN (grade 2-3).
Datas will be updated.
996
Predictors of Postural Control in Cancer Patients Undergoing
Neurotoxic Chemotherapy
Jana Müller1; Maximilian Köppel1; Nikolaus Kleindienst2;
Andreas Schneeweiss3; Markus Weiler4; Joachim Wiskemann1
1National Center for Tumor Diseases (NCT), Working Group Exercise Oncology,
Division of Medical Oncology, Heidelberg, Deutschland
2Central Institute of Mental Health Mannheim, Institute of Psychiatric and
Psychosomatic Psychotherapy, Mannheim, Deutschland
3National Center for Tumor Diseases (NCT), Division Gynecologic Oncology,
Heidelberg, Deutschland
4Heidelberg University Hospital, Department of Neurology, Heidelberg,
Deutschland
Purpose: Postural control (PC) in cancer patients deteriorates during
neurotoxic chemotherapy (NTX), which may be due to altered proprio-
ception. However, clinically diagnosed nerve damage showed only mod-
erate correlations with PC [1]. us, other predictors might exist that in-
uence the change in PC during NTX.
Methods: Fiy-four cancer patients participated in this longitudinal study
(age 54 ± 11 years). PC in semitandem stance with eyes closed (force plate:
center of pressure data), CIPN symptoms (EORTC QLQ-CIPN20), nerve
conduction studies (NCS: motor (CMAP) and sensory action potentials
(SNAP)), quadriceps maximal voluntary contraction (MVC), and phys-
ical activity (PA) were assessed before (t0) as well as 3 weeks (t1) and six
months aer completion of NTX (t2). Time dierences in PC, CIPN and
NCS were determined by dependent t-tests (Bonferroni corrected). e
inuence of CMAP, SNAP, PA and change in MVC (Δt0-t1) on the change
in PC during NTX (Δt0-t1) was analyzed by multiple linear regression
adjusted for age and BMI.
Results: PC, CIPN symptoms and NCS signicantly deteriorated during
NTX (t0-t1: p < .01). Six months aer NTX, patients recovered from pos-
tural instabilities (t0-t2: p = .77), whereas CIPN symptoms and NCS were
still worse compared to t0 (p < .01). e regression model showed that
low baseline CMAP (β = -47.7; p < .01) and high SNAP (β = 25.6; p = .01)
predicted greater loss of PC.
Conclusions: Unexpectedly, good sensory nerve function at baseline pre-
dicted a greater loss of PC during NTX. It can be assumed that disturbed
peripheral sensory information may lead to adaptation processes (neuro-
nal plasticity). erefore, patients with poorer sensory nerve function at
baseline may have been less aected by further deterioration of somato-
sensory feedback as they had already adapted to these impairments. is
hypothesis is supported by follow-up data: Although CIPN symptoms and
CVS were still worse compared to baseline, PC recovered.
Disclosure Statement: No conict of interests.
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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts246
Inhalt
2018
Index
2018
Reference:
1. Müller et al. (2019). Gait Posture (submitted)
1022
Analysis of the Current Status of Exercise Therapy for
Oncological Patients: A Cross-Sectional Survey Among
Resident Oncologists and Physiotherapists in an Out-Patient
Setting
Elisa Zavatta1; F Kron1; Ft Baumann1
1University of Cologne Department I of Internal Medicine Center for Integrated
Oncology Aachen Bonn Cologne Dusseldorf University Hospital of Cologne ,
Cologne, Deutschland
Purpose: e goal of the cross-sectional study conducted in July/ August
2018 in Germany for the rst time simultaneously among resident oncolo-
gists and physiotherapists to identify the benet of special exercise therapy
for oncological patients was to determine the current state of knowledge
of both professions and relevant information for out-patient oncological
care. e analysis was motivated by an obvious discrepancy: While more
and more studies are providing evidence of the positive eects of special
exercise therapy, the care structures have not yet been designed in such a
way that quality-assured exercise programs for oncology patients are of-
fered across the board.
Methods: e collected data, which were generated by a written survey
conducted by the Center for Integrated Oncology (CIO), were evaluated
using descriptive statistical methods. 300 questionnaires were distributed
to both service providers, selected by stratied random sampling. e re-
sponse rate was 21% for oncologists (N=63) and 29% for physiotherapists
(N=88).
Results: e majority of both professions attribute a high value and bene-
t to special exercise therapy and seem to be informed and educated about
the proven positive eects in the major cancer diseases. Larger dierences,
among others, were found in the fatigue topic. While almost all oncolo-
gists (95,2%, n=50) were aware that exercise therapy is the most eective
method for reducing fatigue, this was not true to a comparable extent for
physiotherapists (58%, n=51). e majority of oncologists (98,4%, n=62)
oen recommend a physically active everyday life to their patients and
see an average need of four patients per day for a special exercise therapy
(n=55). e results also provided indications of current barriers to the
expansion of exercise therapy programs.
Conclusions: e results not only inform current discourses about the
goal of a nationwide, guideline-based and quality-assured care structure
in Germany, they also indicate a need for improvement in the expansion
necessary network of oncologists and physiotherapists.
1043
Inuence of Target-Oriented Exercise Therapy on the Fatigue
Syndrome and Strength Capacity in Cancer Patients
Stefanie Siebert1; Timo Niels1; Freerk Baumann1
1Uniklinik Köln - CIO, Köln, Deutschland
Purpose: CRF is the most common side eect of medical treatment in
cancer patients. e ecacy of exercise on cancer induced side eects like
psychological distress is scientically proven. e impacts vary from en-
hanced physical performance to an increased patient compliance and an
improved prognosis of the disease. e present study aimed to determine
the coherence between the increase in strength and psychological distress.
Methods: To examine this coherence, a pre-test and post-test was con-
ducted with the use of machine-supported, supervised training. e
presence of the CRF was evaluated through two assessments (MFI, VAS)
whereas the burden of anxiety and depression was self-reported with
HADS. e study design divides participating patients into ve groups
with dierent workout intensities. Two groups performed an endurance
training and two groups performed a strength training. Group 5 expe-
riences the standard care. 33 aercare patients participated in the study.
Results: e present study shows a high impact of physical exercise on
reducing cancer-related fatigue. Regardless of the intervention group,
73.03% of the participants beneted from the activity. Concerning the
dierent groups, the high-intensity groups showed positive results. Espe-
cially the strength-HIT group needs to be emphasized with every patient
in the group increasing strength whilst reducing the MFI-score, hence re-
ducing fatigue. e study population shows a highly signicant reduction
in MFI-scores.
Conclusions: is result shows the need of initiating interdisciplinary
treatment concepts in order to improve functional health for patients.
Further studies need to prove the sustainable eects of indication-specic
exercise programs, together with verifying the dose-response relationship.
Studies should aim to individualize exercise therapy with respect to sever-
ity of the fatigue-symptoms, personal preferences or resources.
Disclosure Statement: I declare that we have no relevant or material nancial
interests that relate to the research described in this paper.
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Autorenindex
© 2020 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/ort
Inhalt
2018
Index
2018
A
Abbasi-Senger, N. 648, 662
Abdu, A. 377, 398
Abera, S. 583
Abonour, R. 804
Abou-Alfa, G.K. 171, 172, 174, 916
Abramson, J. 976
Abrao Miziara, J.E. 659
Acevedo, A. 1000
Achenbach, M. 235
Acker, F. 266
Adam, S. 64, 65
Adamietz, Irenäus A. 686
Ade, Carsten P. 188
Adebahr, S. 261, 738
Adeberg, S. 37, 519
Adelman, C. 676, 690
Ades, L. 781
Agaimy, A. 130, 595
Agarwal, N. 690
Ahlborn, M. 452, 476
Ahmed, A. 971
Ahn, M.-J. 402, 581, 644, 788, 875
Ahrens, M. 1037
Ai, M. 502
Aigner, C. 464, 604, 606, 635
Akbaba, S. 37
Akewanlop, C. 659
Akilli-Ozturk, O. 900
Akolkar, D. 731
Al-Ahmadie, H. 727
Al-Ali, Haifa K. 529, 692, 700
Al-Batran, Salah-E. 218, 758
Al-Kali, A. 1052
Al-Rajabi, R. 916
Albers, D. 836
Albers, P. 899
Albert, Catherine M. 274
Albert, I. 1008
Albert, Ute-S. 575
Alberter, B. 628
Albertsmeier, M. 199
Albertson, T. 976
Albiges, L. 323, 993
Albrecht, C. 900
Aleric, I. 298
Alexander, J. 886
Algül, H. 199, 218, 382,
404, 822
Ali, M.-D. 1033
Allen, A. 676
Allende, V. 543
Allieu, Roland J. 616
Alt, J. 399, 632
Alt-Epping, B. 143
Alter, M. 816
Altmann, U. 316, 539
Altrock, E. 755
Alwers, E. 661
Amann, K. 600
Ambrosi, G. 149
Amdal, Cecilie D. 570
Amitay, E. 661
Ammerpohl, O. 200
Anapolski, M. 478
Anders, C. 168
Anderson, L. 608
Andorsky, D. J. 963
Andre, F. 330
Andreadis, C. 976
Andric, Z. 884
Andrulat, A. 262
Angele, M. 199
Anthuber, C. 493
Antoch, G. 899
Antonia, Scott J. 579
Antoniou, A. 585
Arkenau, Hendrik-T. 608
Armbrust, R. 576, 684
Armstrong, J. 399
Arnason, J. 976
Arndt, A. 362
Arndt, V. 64, 65, 106, 281, 289,
620, 792, 803
Arnold, A. 933
Arnold, D. 444, 533, 822, 1016
Arnold, G. 335
Arnold, N. 585
Arránz Becker, O. 612
Arsov, C. 899
Arén Frontera, O. 132, 1000
Asberger, J. 310
Ashyrova, F. 833
Aspacher, L. 266
Asperger, H. 757
Ataseven, B. 265
Atkins, M. 993
Attal, M. 482
Au, Kwok H. 242
Aucoin, J. 1000
Audigier-Valette, C. 1000
Augustin, M. 673, 958
Auperin, A. 1053
Aust, D. 288, 641
Avery, E. 183
Awada, A. 168
Axenie, C. 113
Azizian, A. 704, 846
Azoitei, A. 443
Azoitei, N. 200, 287
Álvarez-Twose, I. 742
B
Bach, E. 819
Bachelot, T. 168
Bacher, M. 703
Bachmann, M. 827
Backsch, C. 497
Badenhoop, K. 654
Badmann, S. 893
Baerlocher, Gabriela M. 420
Baert, T. 265
Bagdasarova, D. 829
Baio, G. 172
Balaban, Ü. 654
Baldus, S. 847
Ballmer, Peter E. 251
Bamberg, F. 627, 739
Bamberg, L. 149
Bamias, A. 295
Banaz-Yasar, F. 560
Banerji, V. 236
Bankfalvi, A. 604, 606, 635
Bankstahl, Ulli S. 758
Banna, Giuseppe L. 295
Baran, C. 595
Barenboim, M. 1048
Baretton, G. 288, 641
Barlesi, F. 948, 1000
Barnes, B. 451, 617
Baron, A.D. 174
Barrett, J C. 607
Barriga, S. 328
Barrios, C. 884
Bartels, M. 859
Barthélémy, P. 1037
Bartl, N. 739
Bartsch, Hans H. 134
Bartsch, J. 249
Bartsch, R. 57
Barve, M. 402
Basara, N. 533, 722
Bashir, S. 334
Bassermann, F. 475
Bassy, M. 629
Bast, H. 287
Bauer, C. 390
Bauer, S. 673
Bauer, T. 190
Bauer, W. 141
Bauerfeind, I. 262, 636
Bauernfeind, Franz-G. 194
Bauerschlag, D. 691
Bauerschmitz, G. 269, 363
Bauerschmitz, L. 837
Baum, R. 25
Baumann, D. 263
Baumann, F. 45, 157, 536, 986, 1022
Baumann, K. 123, 523
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Oncol Res Treat 2020;43(suppl 1):1–265 Author Index248
Inhalt
2018
Index
2018
Baumann, M. 960, 1016, 1043
Baumann, R. 194
Baur, A. 55
Baur, I. 494
Baur, M. 37
Bauschke, A. 861
Bausewein, C. 56
Bayer, O. 235
Bear, M. 168
Bechstein, Wolf O. 223, 758
Bechtner, C. 683
Beck, C. 130
Beck, E. 412
Beck, Susanne C. 438, 454
Becker, G. 123
Becker, H. 438
Becker, Jürgen C. 541
Becker, Karl-F. 199
Becker, M. 630
Becker, N. 899
Becker, S. 423, 425
Becker, T. 611, 678, 1051
Beckert, F. 980, 1023
Beckert, S. 769, 834
Beckmann, Jan H. 611
Beckmann, Mathias W. 485
Bedeke, J. 1037
Bedir, A. 998
Bedke, J. 324
Beer, André-M. 252
Begum, N. 703
Beha, J. 400
Behl, N. 519
Behling, F. 965
Behr, B. 307, 331, 388
Behrens, G. 122
Behrens, R. 382
Beielstein, A. 255
Beiersdorf, J. 497
Beifus, K. 1032
Beissbarth, T. 459
Beitzen-Heineke, A. 623, 650
Beißbarth, T. 903
Bekeschus, S. 880
Beksac, M. 482
Belau, A. 691
Belka, C. 262, 367, 555
Belleville, E. 994
Belova, I. 709
Belyaev, O. 646
Belz, H. 324
Bendfeldt, C. 223
Benmebarek, Mohamed-R. 1040
Benner, A. 899
Benner, J. 208
Benzaghou, F. 174
Berdeja, J. 804
Berdel, Wolfgang E. 445
Bergbold, S. 620
Bergelt, C. 143, 623, 650
Berger, M 962, 1033
Bergmann, L. 463, 1037
Berking, C. 889
Berlin, J. 274
Berlin, P. 921
Berling-Ernst, A. 986
Bernd, A. 585
Berndt, K. 333
Berner, K. 310
Bernhardt, C. 394
Bernhardt, D. 37
Bernhardt, M. 704
Bernsmeier, A. 67
Bertram, H. 289, 792, 803
Bertram, L. 642
Bertz, S. 383
Besendörfer, M. 502
Betge, J. 149
Bettina, D. 605
Bettinger, D. 739
Beutel, Manfred E. 597, 666
Beverungen, D. 819
Beyeler, S. 514
Beyer, I. 598
Beyer, S. 893
Bhagavatheeswaran, P. 1008
Bi, X. 715
Biel, A. 1037
Bielack, S. 623, 650
Bietenbeck, A. 475
Bildat, S. 298
Bill, M. 747, 754
Binder, C. 449, 459
Binder, M. 503
Binninger, A. 391
Bipp, T. 695
Birgin, E. 58, 169
Birndt, S. 554, 769, 834
Bischo, H. 411, 607
Bischo, Helge G. 201, 409
Biskup, S. 260, 386, 400
Bislich, Dipl.-Phys. O. 296
Bittner, A. 524
Bittrich, M. 640
Bitzer, M. 400
Bjordal, K. 570
Blanc, J.-F. 117, 172
Blankenstein, C. 199
Blasi, M. 520
Bleckmann, A. 449, 459
Blettner, G. 494
Blettner, M. 501
Bloch, W. 45, 294, 313, 682
Block, A. 673
Blohmer, Jens-U. 588, 615, 636, 694
Bludau, F. 708
Bluhm, J. 467
Blum, Torsten G. 190
Bläker, H. 661
Blüm, P. 475
Blümcke, B. 197
Boccadoro, M. 804
Bochtler, T. 409
Bochum, S. 260
Bockmühl, U. 259
Bodmer, A. 119
Boegemann, M. 1037
Boesten, T. 623, 650
Bogenberger, J. 1052
Bohnenberger, H. 449
Bohnet, S. 411
Bokemeyer, C. 143, 326, 495, 530, 623, 650
Bolenz, C. 383, 443, 546, 610, 634
Bolling, C. 1016
Bolondi, L. 171
Bolotina, L. 783
Bolze, S. 595
Bondarenko, I. 399
Boothman, A.-M. 581
Borad, M. 916
Borchert, S. 190, 604, 606, 635
Borde, J. 585
Bordogna, W. 1009
Borghaei, H. 1008
Borken, F. 613
Born, J. 67
Borner, M. 119
Bornhäuser, M. 609
Boroch, W. 182
Boré, F. 545
Bossart, M. 576
Bourhis, J. 1053
Boutros, M. 149
Boyer, Michael J. 607
Bozko, P. 454
Bozorgmehr, F. 409
Braess, J. 445
Brahmer, J. R. 1008
Brambs, Christine E. 371, 493
Brandt, F. 316, 539
Brandts, C. 223
Braud, F. 948
Brauer, D. 747, 754, 776
Braumann, C. 455, 854
Braun, M. 262
Braun, U. 184, 185
Breder, V. 882
Brederecke, J. 93
Bredow, K. 197
Breidenbach, C. 470, 798
Breitbach, Georg-P. 150
Breitbart, E. 609
Breitenbücher, S. 182
Breitenstein, U. 119
Brenk-Franz, K. 316
Brenner, A. 738
Brenner, H. 122, 176, 281, 289,
349, 352, 568,
661, 792, 803
Brentano, G. 854
Bresadola, L. 900
Breyer, J. 383, 546, 610, 634
Brhel, M. 287
Briest, S. 814
Brigitte, S. 237
Brinkers, M. 408
Brinkhaus, B. 311
Brioli, A. 302, 647
Brockho, G. 153, 540
Brodowicz, T. 1016
Brokstad Herlofson, B. 570
Brons, S. 263
Brossart, P. 194
Bruch, Harald-R. 395
Brucker, C. 272, 576
Brufsky, A. 119
Bruner, C. 329
Brunnberg, U. 266
Brunner, C. 200, 287, 474
Brunner, M. 130, 131
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 249
Inhalt
2018
Index
2018
Brunner, T. 261, 614, 739,
832, 836
Brunotte, S. 720
Bruns, G. 235
Brzezicha, B. 524, 578, 615, 794
Brähler, E. 597
Bröckelmann, P. 889
Brückl, W. 238, 693, 934
Brückner, S. 859, 860
Brümmendorf, Tim H. 420
Buchen, S. 588
Buchholz, D. 124
Buchholz, M. 455
Buchholz, S. 153
Buchholz, T. 147
Buchner, A. 763
Budach, W. 194
Buderath, P. 691
Bukur, V. 900
Bulusu, K. 607
Bumes, E. 506
Bunea, H. 187
Bung, R. 112
Bunse, L. 86
Bunse, M. 467
Bunse, T. 86
Burchert, A. 420
Burdach, S. 1048
Burdaeva, O. 328
Burgents, J. 676, 690
Burger, M. 383, 546, 610
Burgermeister, E. 149
Burges, A. 493, 523,
691, 893
Burgess, E. 488
Burghardt, I. 386, 400
Burkhard, O. 184, 185
Busch, Chia-J. 259
Busch, D. 1048
Buschbeck, M. 613
Busenbender, T. 326
Bushnak, A. 570
Butt, E. 526
Buttmann-Schweiger, N. 671
Byrd, J. 236
Byrne, N. 399
Bäcker, A. 316, 539
Böck, S. 404, 761
Bögemann, M. 324, 391
Böhm, A. 570
Böhme, H. 155
Böthig, R. 155
Böwe, R. 536
Büchler, B. 235
Büchler, M. 433
Bühler, H. 686
Büntzel, H. 333
Büntzel, J. 241, 243, 333,
390, 490
Bürtin, F. 569
Büsche, G. 398
Büssing, A. 123, 241, 243
Büter, T. 605
Büttner, B. 794
Büttner, M. 230
Büttner, R. 484
Büttner-Herold, M. 595
C
Cabos, P. 168
Cadilha, Bruno L. 1040
Calaminus, G. 623, 650
Califano, R. 875, 886
Camey, B. 64, 65
Camidge, D.R. 875
Camidge, R.D. 1009
Cammann, C. 111
Campana, F. 482
Campbell, M. 993
Campbell, P. 183
Campelo, M. 875
Canbay, A. 918
Canjuga, D. 438, 454, 514
Canzler, U. 523, 691
Capitain, O. 1053
Capobianco, I. 538
Capper, D. 386
Carcereney, E. 997
Caro, R. B. 1008
Carr, P. 661
Carvajal, G. 545
Casati, B. 933
Castanie, H. 1053
Castellano, D. 295, 1037
Castro Silva, J. 570
Catenacci, D. 916
Cathomas, R. 495
Catron, K. 330
Catto, J. 727
Cavo, M. 482
C García-Montero, A. 742
Chakupurakal, G. 184
Chalopin, C. 802
Chan, A. 330
Chan, S.L. 117, 171
Chang, C.-W. 995
Chang-Claude, J. 176, 281, 661
Chari, A. 804
Chemnitzer, O. 800
Chen, W. 1019
Chen, Y. 399
Cheng, A.-L. 171, 172, 174, 882, 1019
Cheng, Y. 607, 886
Chermat, F. 781
Cheung, P. 898, 985
Chi, K. 690
Chiabudini, M. 254, 276
Chiappori, A. 579
Chikhradze, N. 605
Childs, Barrett H. 274, 282
Chin, K. 788
Chittka, D. 153
Chiu, Chao-H. 242
Chmielecki, J. 607
Cho, B.C. 581, 644
Cho, Byoung C. 402, 579, 607, 788
Choeurng, V. 995
Choi, YD. 676
Choo, J. 528
Choueiri, Toni K. 132, 323, 993
Chowdhury, S. 372
Choy, E. 295
Christ, B. 859, 860
Christalle, E. 465
Christiansen, H. 782
Christoph, D. 635
Christopoulos, P. 201, 374, 393, 409,
520, 934
Christy-Bittel, J. 608
Chruscz, D. 797
Chu, K. 900
Chudasama, P. 112, 613
Chudnovsky, A. 993
Chun, F. 1023
Ciardello, F. 608
Ciardiello, F. 586
Cicin, I. 171
Ciuleanu, T. 1000
Clasen, N. 914
Classen, C. F. 623, 650
Clauß, K. 539
Clay, T. 997
Clement, J. 809
Collenburg, L. 55
Collienne, M. 444
Combs, S. 199, 367, 475, 1023
Combs, Stephanie E. 262
Conev, Nicolay V. 399
Conkling, P. 586
Conte, PierF. 328
Conte, Pierre F. 168
Cony-Makhoul, P. 781
Cook, G. 804
Corbett, G. 236
Corcoran, C. 676
Cornelius, Jan F. 658, 660
Corradini, S. 836
Cortesi, F. 551
Corzo, Kathryn P. 482
Costa, Serban D. 119
Costantino, J. 694
Costello, C. 804
Couch, Fergus J. 636
Coutre, Steven E. 236
Cox, Michael C. 274, 282
Cramer, T. 689
Crispin, A. 264
Crodel, C. 214
Croner, Roland S. 220, 221, 512, 515
Cross, M. 529, 819
Cross, N. C. P. 742
Cross, Nicholas C. P. 744
Crysandt, M. 673
Cui, K. 822
Cunningham, D. 1016
Cupissol, D. 1053
Cymbalista, F. 236
Czemmel, S. 514
Czogalla, B. 893
Czuczman, M. 963
Czwikla, J. 88
D
Dadduzio, V. 171
Dadras, M. 307, 331, 388
Däggelmann, J. 294, 313, 682
Dahlmann, M. 794, 799, 853
Dahm, S. 451
Dahm, T. 533
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Oncol Res Treat 2020;43(suppl 1):1–265 Author Index250
Inhalt
2018
Index
2018
Dahmen, U. 859, 860, 861
Dall, K. 678
Dammermann, W. 648
Daniel, Davey B. 579
Daniele, B. 172
Danner, J. 755
Danzer, E. 595
Dargatz, P. 463
Darsow, M. 984
Darwiche, K. 464
Datar, R. 731
Datta, V. 731
David, S. 82
Davies, F. 804
De Back, W. 288, 641
de Bono, J. 676, 690
De Castro Carpeno, J. 886
de Ducla, S. 295
De Giorgi, U. 295
De Gregorio, A. 215
de Gregorio, N. 523, 691
De la Serna, J. 183
de la Mora Jimenez, E. 1008
De Porre, P. 372
De Renzis, B. 781
de Wit, M. 581, 579, 640
de Zwaan, M. 237
Debus, D. 816
Debus, J. 216, 263, 519, 672
Debus, Jürgen P. 37
Dechow, T. 276, 392
Decker, T. 119, 254, 405, 452,
476, 756, 994
Degenhardt, T. 771
Deike-Hofmann, K. 519
Deis, N. 125
Del Chiaro, M. 433
Delmonte, A. 875
Delhommeau, M. 1053
delorme, thierry. 545
Demetri, G. 586, 991
Dempf, A. 1047
Deng, Y. 886
Denisova, E. 613
Deniz, M. 772
Denker, S. 524
Denkert, C. 142, 588, 629, 694
Dennis, L. 995
Dennis, Phillip A. 579
Denschlag, D. 691
Depenbusch, J. 256
Deppermann, Karl-M. 484
Deprince, K. 488
Derevyanko, P. 528
Deryal, M. 270, 272
Desai, J. 608
Deshpande, A. 111
DI Pietro, A 993
Diallo, T. 627
Diebolder, H. 669
Diehm, Y. 962
Dieke, M. 618
Diel, I. 257
Diener, M. K. 971
Dieng, S. 470, 798
Dierkes, S. 198
Diermeier-Daucher, S. 153
Diestelhorst, A. 599
Dietrich, P. 931
Dietrich, S. 188
Dietz, A. 194, 259
Dietz, S. 374
Dietzel, C. 170, 414
Dimicoli-Salazar, S. 781
Dimopoulos, M. 482
Dinkel, A. 144
D‘ippolito, E. 1048
Dippel, S. 797
Dirksen, U. 203, 623, 650
Dittmar, G. 853
Dobbelstein, M. 528
Doebele, R. 402, 586, 991, 992,
995, 948
Doege, D. 106, 289, 792, 803
Doescher, J. 287
Doger, B. 997
Doki, Y. 788
Dolan, S. 183
Dondorf, F. 861
Donegan, S. 727
Donskov, F. 132
Dörfel, S. 391, 426
Dörje, F. 567
Dorman, K. 1040
Dornstauder, E. 257
Dörr-Harim, C. 971
Döscher, J. 200, 397, 474
Dotan, E. 916
Doz, F. 274, 282
Dr. Jansen, H. 1047
Dr. Wahl-Wachendorf, A. 74
Draeger, N. 755
Draeger, T. 466, 748, 749, 750, 751
Dräger, Desiree L. 147, 148
Drees, R. 200, 287
Drewniock, P. 722
Driemel, C. 849
Driesen, J. 162
Drilon, A. 274, 282, 402, 948,
992, 995
du Bois, A. 265
Duadze, I. 829
Dubey, S. 171
Düber, C. 999
Dubin, F. 482
Dubois, Pierre Y. 545
DuBois, Steven G. 274, 282
Dubos Arvis, C. 1053
Dück, M. 412
Ducreux, M. 882, 1016
Duda, Dan G. 738
Dudys, P. 362
Dueck, A. 1052
Dünser, J. 287
Dupoiron, D. 545
Duran, I. 295
Dürr, P. 567
Dürst, M. 446, 497, 669, 837, 1035
Dutz, S. 809
Dwinger, S. 623, 650
Dyshlovoy, S. A. 326, 530
Dziadziuszko, R. 991, 992, 995, 1009
E
Eberhardt, B. 958
Eberhardt, J. 582
Eberhardt, W. 464, 604, 606, 635, 190
Eberhardt, Wilfried E E. 393, 394, 395
Eberle, A. 289, 792, 803
Ebert, Matthias P. 149
Eble, M. 194
Echarti, A. 929
Eckel, R. 361
Eckert, Alexander W. 723
Eckhardt, C. 251
Eckstein, M. 383, 546, 610, 634
Edler von Koch, F. 493
Efanov, V. 829
Egberts, Jan-H. 611
Egerer, G. 458
Eggensberger, T. 504
Egger Hayoz, C. 64, 65
Egger, E.K. 1029
Eggers, H. 335, 563, 782
Eggersmann, T. 771
Egle, D. 119
Egyed, M. 236
Ehmann, S. 265
Ehret, F. 37
Ehscheidt, P. 184, 185
Eichmüller, Stefan B. 263
Eickenscheidt, A. 187
Eickho, R. 689
Eigentler, T. 320
Einsele, H. 392, 956
Eischen, C. 528
El-Balat, A. 211, 423, 425, 523, 691
El-Khoueiry, A.B. 117, 171, 174
Ell, J. 375
Ellis, P. 226
Elmers, S. 623, 650
Emmert, S. 880
Emons, G. 269, 363
Enatsu, S. 242
Ender, F. 580, 637
Endres, S. 1040
Endris, V. 374, 409
Engel, C. 585, 814
Engel, J. 262, 300, 361, 367, 491, 493
Engelhardt, M. 392, 448
Engelmann, B. 157
Engel-Riedel, W. 659
Englert, J. 322
Enßle, J. 266
Enquist, I. 884
Enz, N. 630
Erben, P. 383, 546, 610, 634
Erbes, T. 310
Erdmann, G. 149, 334, 362
Erdmann, M. 889
Erices-Leclercq, M. 847
Erickson, N. 124, 251
Erkut, C. 112
Erler, T. 446
Ermoshenkova, M. 775
Ernestus, Ralf-I. 789
Ernst, C. 162, 585
Ernst, G. 317
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 251
Inhalt
2018
Index
2018
Ernst, M. 597
Ernst, T. 302, 420, 486, 526, 744
Escudier, B. 1037
Escherich, G. 623, 650
Esser, K. 766
Esser, R. 1019
Ettl, J. 168, 330
Ettl, T. 387, 410
Ettrich, Thomas J. 218, 382, 404
Evdokimova, V. 1048
Even, C. 1053
Evers, C. 544
Evert, K. 387, 410
Eze, C. 555
Ezić, J. 200, 474
F
Fabarius, A. 742
Faber, G. 165
Faber, J. 45, 501, 597, 623, 650, 941
Faber, N. 722
Fabian, A. 570
Fabisch, C. 420
Faehling, M. 409, 579
Falk, M. 181, 464, 594
Faller, H. 623, 650
Farago, Anna F. 274, 282, 402, 992, 995
Farrelly, E. 804
Fasching, Peter A. 142, 215, 232 588,
629, 636, 694, 994
Fear, S. 295
Fechner, K. 1027, 1028
Feder, I. 533
Fegeler, C. 260
Fehlauer, F. 296
Fehm, T. 215, 582, 598, 628, 757,
766, 849
Fehn, A. 474
Feiten, S. 184, 185
Feith, M. 199
Felgendre, P. 859, 861
Felip, E. 997, 1000
Féliz, L. 916
Feller, A. 65
Fenaux, P. 781
Fenk, R. 956
Ferencz, J. 470
Ferenczy, P. 404
Fernández Moro, C. 433
Fernandez-Pacheco, M. 657
Ferro, S. 727
Fett, S. 432
Fetzer, A. 462
Feuersinger, D. 112
Feufel, M. 1027, 1028
Fey, T. 251
Feyerabend, S. 690
Fichter, C. 458
Fichtner-Feigl, S. 403, 627, 631, 840
Ficker, J. 238, 693, 934
Fiebag, K. 155
Fieber, V. 462, 609
Fiebig, J. 369
Fietkau, R. 929
Fietz, T. 458
Finke, I. 122, 568
Finkeisen, D. 260
Finn, R. 882
Fischbach, F. 832
Fischbach, K. 832
Fischer, H. 346, 1032
Fischer, J. 849
Fischer, Jürgen R. 409, 1000
Fischer, Lotta A. 552
Fischer, M. 673
Fischer, S. 962
Fischer, T. 529
Fischer von Weikersthal, L. 276, 452, 476,
756, 958
Fischer-Jacobs, J. 231, 237
Fizazi, K. 249, 676, 690
Flach, J. 755
Flebbe, H. 812
Flechtenmacher, C. 37
Fleischmann, D. 170
Fleischmann, M. 554
Fleitz, A. 393, 394, 395
Flentje, M. 1023
Flessner, F. 706
Flohr-Schmitt, E. 235
Flörcken, A. 463
Florschütz, A. 529
Fodi, Christina-K. 965
Fogliatto, Laura M. 236
Follows, G. 236
Folprecht, G. 586, 608, 991
Foran, J. 1052
Fontecedro, A.C. 1000
Forrester, Tammy D. 167
Forschner, A. 431
Förster, F. 847
Fottner, C. 703
Fragoulis, A. 689
Franck, C. 918
Frank, F. 287
Franke, Georg-N. 744, 776
Franken, A. 582, 628, 849
Frank-Gleich, S. 382
Franz, K. 379
Franz, W. 156
Freemantle, N. 174
Freidank, A. 198
Freitag, A. 591
Freitag, D. 648, 649, 584, 662
Frenzel, M. 328
Frerichs, W. 457, 573
Freudlsperger, C. 37
Freund, E. 880
Freund, M. 165
Frick, E. 243
Frick SJ, E. 241
Friederich, Hans-C. 26, 375
Friedl, Thomas W. P. 215, 772
Friedrich, M. 86
Fries, H. 776
Friesenhahn, V. 184
Friess, H. 199, 367
Frietsch, J. 526
Frimodt-Moller, B. 242
Fritz, Eva-M. 148
Fritz, G. 126
Fröhlich, R. 598
Fröhling, S. 112, 613
Fromm, Martin F. 567
Fu, M. 488
Fuchs, F. 889
Fuchs, J. 131
Fuchs, M. 404
Fügemann, H. 314
Furich, N. 383
Furlanetto, J. 142, 629, 636
Fürst, A. 466, 749, 750
Fuxius, S. 452, 476
G
Gademann, G. 614
Gadgeel, S. 1009
Gaedcke, J. 704, 812, 846
Gaertner, S. 126
Gagliani, N. 551
Gainford, C. 330
Gaisa, Nadine T. 763
Gajda, M. 497
Galle, P. 882, 999
Gallinson, D. 916
Galsky, M. 727
Gambara, G. 334
Gamper, E. 230
Gamulin, M. 295
Ganser, A. 337, 563, 782
Ganzert, C. 301
Garassino, M. C. 886
Garcia del Muro, X. 295
Garcia, J. 976
García-Alfons, P. 608
Garczyk, S. 763
Garon, E. 242
Garrido, P. 402, 586
Garrido-Laguna, I. 586
Gaser, D. 396, 968
Gassmann, H. 1048
Gassner, S. 310
Gastinger, I. 221, 512, 515, 516, 517
Gauler, T. 194, 259
Gautschi, O. 607
Gebauer, J. 623, 650
Geater, S. 884
Gebauer J. 623, 650
Geczi, L. 295
Gedye, C. 295, 676
Geese, W.J. 1008
Geier, B. 452, 476
Geisen, R. 678
Gelse, N. 235
Genest, F. 157
Gennari, P. 843
Gennen, K. 555, 557
Geoerger, B. 274, 282
Georois, G. 1053
George, S. 132, 323
Gepfner-Tuma, I. 407, 965
Geppert, C. 131, 600
Geppert, Carol I. 383
Gerard, Camille L. 816
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Oncol Res Treat 2020;43(suppl 1):1–265 Author Index252
Inhalt
2018
Index
2018
Gerber, B. 636
Gerken, M. 122, 378, 466, 478, 485, 487,
657, 748, 749, 750, 830, 913
Gerlach, C. 574
Germer, Christoph-T. 404
Gerthofer, V. 835, 848
Gettinger, S.N. 875
Geuter, U. 842
Geyer, C. 694
Ghadimi, B. M. 812
Ghadimi, M. 846, 704
Ghia, P. 183, 236
Ghiorghiu, D. 727
Ghosh, M. 454
Ghosh, N. 976
Giaccone, G. 884
Giagounidis, A. 781
Giansanti, C. 528
Giesel, Frederik L. 216
Gieseler, F. 580, 637
Giesler, Juergen M. 246, 566
Giordano, F. 708
Gkika, E. 261, 738, 739
Glausch, M. 462, 609
Gleiber, W. 395
Gloaguen, S. 781
Glowik, R. 211
Gockel, I. 759, 800, 802
Gödde, K. 314
Goebell, Peter J. 391, 873
Goel, S. 330
Goerling, U. 304, 314, 428
Goertz, O. 307, 388
Goessl, C. 676, 690
Goetz, L. 269
Gohlke, B. 853
Gökkurt, E. 218, 404
Golan, T. 822
Goldberg-Bockhorn, E. 287
Goldman, J. 399, 659
Goldmann, K. 747, 754
Goldschmidt, H. 115
Golka, K. 155
Golla, A. 441, 503, 599
Gollerkeri, A. 608
Göppner, D. 320
Görlich, D. 445
Gosslau, A. 146
Gotlib, J. 742
Goto, K. 402
Gottardi, E. 744
Gottlieb, T. 765
Götze, K. 781
Götze, T. 218, 758
Götzel, K. 800
Goupil, M. 1037
Gourin, Marie-P. 781
Gouzoulis-Mayfrank, E. 575
Govindarajan, P. 514
Grab, D. 493
Grabmeier-Pstershammer, K. 141
Grabowski, J. 684
Grabowski, Jacek P. 211
Grabowski, M. 220
Grabowski, P. 703
Grade, M. 704, 812
Graefen, M. 530
Graeven, U. 963
Graf La Rosée, P. 420, 769, 834
Gra, S. 913
Gräfe, C. 809
Gräfen, M. 326
Gra, Julie N. 372
Gramann-Weschke, K. 250
Grah, C. 394
Grapp, M. 375
Grassili, E. 200
Gravis, G. 993, 1037
Gray, Jhanelle E. 579, 607
Grebhardt, S. 458
Green, A. 541
Green, E. 86
Greif, P. 461
Greinke, C. 497
Gresing, L. 809
Greve, J. 287
Griesinger, F. 181, 393, 394, 395, 464,
484, 594, 652, 797, 875
Griesshammer, M. 1051
Gri, S. 190
Griths, S. 226
Grigoleit, U. 912
Grillenberger, A. 686
Grilley-Olson, Juneko E. 282
Grimm, D. 845
Grimm, J. 747, 754
Grimm, Marc-O. 132, 323, 324, 1037
Grischke, E.-M. 167, 328, 523, 629
Griss, J. 141
Gröber, H. 575
Groden, C. 755
Groen, H. 594
Groh, S. 147
Grohé, C. 703
Gropp-Meier, M. 523, 691
Grosch, H. 520
Gröschel, A. 472
Groß, Sophie E. 575
Grossert-Leugger, A. 842
Groß-Kunkel, A. 575
Grosu, Anca-L. 194, 261, 738, 739
Grothey, A. 608
Grube, M. 640
Grube, S. 492
Gruber, J. 846
Gruenwald, V. 323
Grüllich, C. 26, 391, 463
Gründker, C. 269, 363
Grünwald, V. 324, 335, 391 463, 563,
632, 673, 782, 958
Grusdat, N. 547
Grützmann, R. 130, 131, 341, 389, 820
Gschwend, J. 495, 899
Gschwend, Jürgen E. 144
Gu, L. 374
Gu, Y. 579
Guenther, M. 761
Guigay, J. 1053
Gundelach, T. 772
Günes, C. 443
Günther, M. 489
Guntinas-Lichius, O. 317, 446
Gupta, A. 727
Guren, Tormod K. 608
Guricova, K. 763
Guth, D. 303
Gütz, S. 472
Gutzmer, R. 320, 563, 889
H
Haalck, T. 816
Haanen, J. 993, 1037
Haas, M. 761
Haase, R. 547
Haberkorn, U. 216, 672
Häberle, L 994
Häberlin, J. 322
Habermann, J. 623, 650
Habisch, P. 780
Hackanson, B. 276
Hackert, T. 971
Hadaschik, B. 899
Hadaschik, Boris A. 372
Hadizadeh, D. 194
Haefner, M. 37
Haefner, Matthias F. 216
Haefner, N. 669, 837
Haferkamp, S. 320, 816
Haferlach, T. 742
Haner, I. 452, 476
Häfner, Hans-M. 431
Hager, L. 316, 539
Hager, T. 604, 606, 635
Hahlweg, P. 457, 465, 573, 587
Hahn, D. 259, 632
Hahn, F. 999
Hahn, S. 455, 901
Hahne, A. 231
Hahnen, E. 142, 162, 197, 585
Hain, L. 648, 662
Hajek, R. 804
Hakenberg, O. 147, 148
Halfter, K. 361
Hall, Michael J. 822
Halle, M. 986
Hallek, M. 255
Haller, B. 199
Hamamoto, Y. 788
Hamdan, Feda H. 812
Hammel, P. 822
Hammers, Hans J. 323
Hammersen, J. 647
Han, J.Y. 875
Handke, U. 743
Hänel, M. 420
Hänggi, D. 655, 658, 660
Hanker, L. 523, 691
Hansel, A. 446, 497, 1035
Hansen, Finn K. 759
Hanslmeier, T. 26
Hanusch, C. 142, 303, 588, 636, 694
Hapfelmaeier, A. 845
Hapke, G. 632
Harati, K. 307, 331, 388
Harbeck, N. 254, 262, 461, 771
Harbeck Petra-D. 623, 650
Harde, J. 405, 458
Harder, T. 645
Hardtstock, F. 57
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 253
Inhalt
2018
Index
2018
Häring, S. 1027, 1028
Harms, J. 93
Harms, L. 93
Harnischfeger, N. 143
Harrison, Michael R. 132
Harter, P. 265, 523, 576, 691
Hartkopf, A. 211
Hartlapp, I. 404
Hartmaier, R. 607
Hartmann, A. 383, 546, 610, 634, 1037
Hartmann, L. 263
Hartwig, M. 41
Hasenauer, J. 476
Hasenburg, A. 1007
Hasenkamp, J. 194, 632
Hass, P. 301, 614, 832, 836
Hassas, D. 485
Hassel, J.C. 889
Hatzipanagiotou, M. 835
Hatzipanagiotou, Maria E. 504
Hauber, Hans-P. 444
Hauer, P. 830
Haug, U. 88, 152, 638, 688
Hauke, J. 142, 162, 197, 585
Hauschild, A. 856
Hauschild, J. 326, 530
Häussler, Ragna S. 149
Haussmann, A. 256
Hauswald, H. 672
Hautmann, M. 194, 387, 506
Hautmann, Matthias G. 410
Havel, L. 399
Haybäck, J. 301, 334
Hazra, S. 174
Hebart, H. 183
Hebestreit, N. 340
Heck, M 980
Heckel, T. 188
Hege, K. 956
Hegedus, B. 604, 635
Hegedüs, B. 606
Hegenbart, U. 529
Hegewisch-Becker, S. 608, 1016
Hehlmann, R. 420
Heidel, F. 111, 214, 302, 613
Heidenreich, S. 797
Heilmann, V. 303
Heim, D. 420
Heimann, M. 194
Heimbach, D. 398
Heimes, Anne-S. 1007
Heine, K. 221
Heine, R. 793
Heinemann, V. 124, 251, 404, 428,
461, 687, 756, 761
Heinicke, T. 529
Heinig, M. 152
Heinrich, B. 119
Heinrich, G. 552
Heinrich, K. 687
Heinrichs, S. 459
Heinsch, M. 912
Heintges, T. 756
Heise, D. 333
Heiser, C. 475
Heisser, T. 349, 352
Heitz, F. 265
Held, T. 37, 433
Hell, S. 819
Hellinger, J. 269, 363
Hellmann, M. D. 1008
Hellmis, E. 463
Helms, M. 891
Hemetsberger, M. 57
Hempel, M. 860
Hendricks, A. 67, 678
Hengstler, H. 834
Henke, M. 187
Henkes, M. 769, 834
Henn, S. 339
Henne-Bruns, D. 897
Henneke, L. 859
Hennes, E. 404
Henninger, N. 45, 501
Hensen, B. 782
Hentrich, M. 640
Hentschel, L. 489
Herber, M. 320, 324
Herbst, R.S. 659, 884
Herbst, R. 781
Herfarth, K. 37, 216, 672
Hering-Schubert, C. 619
Herishanu, Y. 236
Herkommer, K. 144, 899
Hermann, S. 138, 256, 620
Hermes, B. 673
Hernandez, S. 882
Herold, N. 197
Herold, T. 464, 604, 606, 635
Herpel, E. 661
Herrlinger, U. 407, 499
Herrmann, A. 526
Herrmann, C. 64, 65
Herrmann, S. 403, 631
Herschbach, P. 428
Hertel, H. 778, 815
Herter, P. 334
Herth, F. 409, 520
Herz, S. 550, 552, 559, 774
Herzog, T. 533, 854
Hess, V. 842
Hesse, J. 303
Heßler, S. 619
Hessling, B. 149
Heßling, J. 379
Hester, A. 801, 893
Hecht, M. 929
Hetjens, S. 169
Hetterich, M. 378, 478, 504, 843
Heublein, S. 893
Heuer, T. 382
Heukamp, Lukas C. 181, 464, 594
Heußel, Claus P. 201
Heuschmann, P. U. 623, 650
Heussel, Claus-P. 409, 520
Heußner, P. 445
Heutink, P. 514
Heydenreich, M. 342, 350, 353, 355, 356,
357, 358, 359, 364, 368, 547
Heyder, U. 793
Heymach, J. 644
Heymanns, J. 184
Hickstein, L. 257
Hiddemann, W. 445
Hielscher, C. 303, 458
Hiemer, S. 82
Higgs, B. 644
Hilgendorf, I. 302, 554, 623, 650, 813
Hilger, R. A. 914, 950
Hille, A. 776, 819
Hillemanns, P. 523, 548, 691, 778, 815
Hiller, W. 533
Hilpert, F. 211, 523
Hilton, John F. 330
Hilton, M. 1009
Himsel, D. 420
Hingst, H. 73
Hinke, A. 218, 463
Hinsenkamp, I. 149
Hinz, S. 678
Hipp, M. 387, 410
Hipper, A. 393, 394, 395, 673
Hirsch, S. 625
Hirschfeld, M. 310
Hirschfeld, S. 155
Ho Li, J. 399
Hochhaus, A. 156, 214, 302, 420, 486,
526, 529, 554, 647, 744,
769, 809, 813, 834
Hochhauser, D. 822
Hochmair, Maximilian J. 399, 875
Hodge, R. 411, 607
Hoefert, S. 268
Hoenes, S. 914
Hoknecht, P. 394, 934, 1009
Homann, C. 526
Homann, F. 317
Homann, J. 578, 615
Homann, S. 264
Homann, Thomas K. 200, 287, 329,
474, 397,
Homeister, M. 176, 281, 349, 352, 661
Hofmann, Wolf-K. 742, 755
Hogan, W. 1052
Hogrefe, C. 405
Hohenberger, P. 169
Hohmann, D. 257
Höhn, Anne K. 371, 373
Holch, J. 199, 687
Holderried, T. 499
Holland-Letz, T. 216
Hollebecque, A. 916
Holleczek, B. 122, 289, 792, 803
Holmberg, C. 246, 314
Hölscher, T. 557, 787
Holtkamp, U. 494
Holtved, E. 788
Hölzel, D. 300
Holzner, B. 692
Homann, S. 646
Homm, A. 600
Hommann, M. 25
Honarnejad, K. 848
Hong, David S. 274, 282
Hong, Y. 608
Honisch, E. 598, 628
Hönscheid, P. 288, 641
Höpken, U. 467
Horak, P. 112
Hörl, C. 367
Horn, J. 706
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Oncol Res Treat 2020;43(suppl 1):1–265 Author Index254
Inhalt
2018
Index
2018
Horn, L. 886
Horn, Lars-C. 371, 373
Horneber, M. 134, 494, 642, 743
Hornung, M. 830
Horny, Hans-P. 742
Hörsch, D. 25
Horvath, J. 585
Hotta, K. 399
Houet, L. 270, 272, 392
Hoyer, H. 497
Hsu, Chen-J. 613
Hsu, Chih-H. 788
Hsu, L. 176
Huang, B. 993
Huang, H. 804
Huang, X. 402, 586, 948, 991, 992
Hübel, K. 421
Huber, O. 531
Huber, Rudolf M. 780
Huber, S. 551
Hübner, A. 958
Hübner, G. 599
Hübner, J. 316, 339, 490, 539
Huddart, R. 488
Hügle, U. 382
Hühns, M. 569
Hui, R. 579
Humpe, A. 640
Hums, Anna-B. 446
Hünermund, K. 184
Hunger, R. 816
Hunziker, S. 842
Huober, J. 119, 215, 588, 636, 694
Huppertz, S. 649
Hurt, K. 328
Husmann, G. 223
Hussain, M. 676, 690
Hütter-Krönke, Marie-L. 781
Hutzschenreuter, U. 458
Huynh, D. 1040
Hyman, David M. 274
I
I Muñoz-González, J. 742
Iben, S. 443
Idler, C. 793
Ignatov, A. 360, 378, 478, 657, 843, 913
Ignatov, T. 360
Ihorst, G. 448, 739
Ihrig, A. 26, 71, 235
Ikeda, M. 882
Ilgen, J. 699
Illes, A. 183
Im, Seock-A. 330
Imamura, F. 242, 607
Imkamp, F. 488, 899
Inhestern, J. 570
Inoue, K. 328
Investigators, N. 119
Inwald, Elisabeth C. 470, 478, 487, 657, 913
Ishii, Y. 132
Isselhard, A. 1032
Ivanyi, P. 324, 335, 337, 463,
563, 632, 673, 720,
782, 958, 1037
Izbicki, Jakob R. 551
Izquiero Alvalrez, E. 255
Izumi, R. 236
J
Jabbar, F. 735
Jablotschkin, M. 134
Jackisch, C. 142, 523, 588, 636, 694
Jacob, A. 183
Jacob, J. 257
Jacobasch, L. 214, 958
Jaeger, A. 845
Jaehde, U. 489
Jäger, B. 849
Jäger, E. 151
Jäger, M. 310, 823
Jahn, B. 543
Jahn, P. 494
James, N. 295
Jänicke, M. 254, 391, 392, 393,
394, 395, 426
Jann, Johann-C. 755
Janni, W. 215, 683, 772
Jansen, L. 122, 281, 289, 446, 568,
661, 792, 803
Jansen, V. 167
Jansen-Winkeln, B. 802
Jansho, A. 459
Janssens, A. 236
Jao, K. 1000
Jaoul, vir. 545
Jarczyk, J. 546, 610
Jassem, J. 884
Jawhar, A. 755
Jawhar, M. 742
Jechorek, D. 827
Jefremow, A. 889, 931
Jelas, I. 348
Jens Peter, von K. 853
Jens, S. 965
Jensen, W. 623, 650
Jentschke, E. 695, 789
Jentschke, M. 548, 778
Jentsch-Ullrich, K. 214
Jentzsch, M. 747, 754, 819
Jersemann, K. 781
Jeschke, U. 801, 893
Jesinghaus, M. 112
Jeske, S. 474
Jeske, Sandra S. 329
Jiang, H. 399, 652
Jiao, L. 689
Jo, P. 704
Jochemsen, A. 528
Jöckel, Karl H. 541
Joechle, K. 403, 631, 840
John, H. 64, 65, 793
John, T. 659, 992
Johnsen, Steven A. 812
Johnston, S. 328, 330
Jöhrens, K. 578
Jonasova, A. 781
Jones, Rober H. 160
Joos, A. 251
Joos, F. 321
Joos, S. 494, 642
Jordan, J. 576
Jordan, K. 115
Jost, P. 980
Joy, S. 793
jubier Hamon, S. 545
Juhasz-Böss, I. 150
Juhasz-Böss, S. 150
Jundt, F. 157, 188
Jung, A. 461, 687, 756
Jung, C. 125
Jungberg, P. 303
Jungbluth, T. 93
Jünger, C. 597
Junghanß, C. 529
Jungmann, P. 150
Jungraithmayr, W. 630
jurczak, W. 183, 236
Jürgens, H. 203
Jurmeister, P. 615
Just, M. 119
Jütte, H. 533, 546, 610, 634
K
Kaaks, R. 899
Kaatsch, P. 941
Kadhum, T. 155
Kadowaki, S. 788
Kahl, C. 529, 756
Kahlmeyer, A. 873
Kähler, K. 856, 889
Kähnert, H. 346
Kaiser, A. 531
Kaiser, I. 818
Kaiser, L. 449
Kajtazi, Y. 535
Kajueter, H. 541
Kaldate, R. 117
Kal, R. 492, 584, 648, 649, 662
Kalfors, M. 226
Kalla, J. 769, 834
Kallage, V. 559
Kalmbach, N. 891
Kalpinskiy, A. 833
Kaltenbach, K. 965
Kaltenstadler, M. 830
Kalusche-Bontemps, Eva-M. 346
Kamdar, M. 236
Kämmerer, D. 25, 535
Kämmerer, U. 321, 338
Kamp, Marcel A. 655, 658, 660
Kampers, J. 548
Kang, J. 690
Kantelhardt, Eva J. 583, 700
Kanz, F. 322
Kaplan, P. 183
Kappler, M. 723
Kappler, P. 337, 720
Kaprin, A. 833
Karagiannis, E. 614
Karapetis, Christos C. 402
Karatas, A. 393, 394, 395
Karg, N. 693
Kargus, S. 37
Kari, V. 812
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 255
Inhalt
2018
Index
2018
Karlsson, K. 236
Karn, T. 629
Karthaus, M. 303, 1016
Karwe, V. 581
Kaschdailewitsch, E. 793
Kaseb, A. 882
Kaskel, P. 797
Käsmann, L. 555, 557, 787
Kaspar, S. 199
Kasper, C. 392
Kasper-Virchow, S. 1019
Kasper, S. 898, 985
Kast, K. 588, 814
Kastner, Anna M. 231
Katalinic, D. 298
Kato, K. 788
Kauertz, K. 203
Kaumann-Guerrero, D. 780, 779
Kaufman, P. 328
Kaufmann, A. 155, 645
Kaufmann, R. 654, 823
Kaune, M. 326, 530
Kayali, M. 162
Kazarnowicz, A. 399
Kazaryan, L. 829
Kazdal, D. 409
Keberle, S. 494
Keck, B. 383
Keck, T. 758
Keilholz, U. 428, 615, 794, 1053
Keinki, C. 316, 490, 539
Keiser, T. 396
Keller, M. 684
Keller, R. 404
Keller-Stanislawski, B. 889
Kelley, R.K. 117, 171, 172, 174
Kellner, M. 257
Kemmler, G. 230
Kendel, F. 1027, 1028
Kennedy, V. 742
Kerle, I. 475
Kersten, J. 960
Kersting, S. 341, 389, 820
Keßler, Almuth F. 789
Kesting, M. 595, 600
Kesting, S. 396, 968
Kettelgerdes, A. 494
Kettelhoit, N. 550, 774
Keyver-Paik, M.- D. 1029
Khil, L. 541
Kiani, A. 756
Kiechle, M. 262, 493, 814, 845, 986, 1047
Kiewe, P. 214
Kilian, M. 86
Kim, Dong-W. 402, 875, 1009
Kim, H.R. 875
Kim, S.-W. 611, 659, 1008
Kim, Y. 976
Kim, Sung-B. 330, 788
Kim, Tae-Y. 882
Kimmig, R. 523
Kindler, Hedy L. 822
Kindler, T. 574
Kirchner, B. 903
Kirchner, M. 409
Kirchner, T. 461, 687, 756, 761
Kirkpatrick, J. 111
Kirner, Julius A. 188
Kirschner, A. 1048
Kirste, S. 739
Kisro, J. 214
Kitagawa, Y. 788
Kitz, J. 704, 812
Kiver, V. 615
Klaassen-Mielke, R. 533
Klafke, N. 642, 793
Klapdor, R. 778, 815
Klar, E. 569
Klare, P. 303, 636
Klatt, P. 743
Klaus, Anne-K. 311
Kleber, G. 382
Kleboth, K. 184
Kleemann, J. 823
Kleilein, J. 589
Klein, Christoph A. 848
Klein, E. 115, 845
Klein, I. 404
Kleindienst, N. 996
Kleine-Tebbe, A. 683
Klemperer, D. 494
Klinghammer, K. 578, 632
Klinkhammer-Schalke, M. 153, 378, 466, 478,
485, 487, 657, 748,
749, 750, 830, 913
Klock, A. 840
Klöckner, R. 999
Kloft, C. 49
Kloor, M. 661
Klotz, D. M. 950
Klotz, R. 971
Klug, S. 432
Klümpem, H.J. 171
Klusmann, I. 528
Knapp, O. 994
Knauf, W. 392
Knauss, S. 889
Kniemeyer, O. 317
Knipps, J. 655, 658, 660
Knobloch, S. 478
Knödler, S. 557
Knötgen, G. 605
Knüchel, R. 763
Ko, Yon-D. 489
Kobelt, D. 799, 853
Kobold, S. 1040
Koch, B. 377, 398, 623, 650
Koch, C. 223
Koch, M. 438, 514
Koch-Gallenkamp, L. 289, 792, 803
Kochenderfer, J. 956
Kodani, M. 788
Koepp, P. 331
Koerber, Stefan A. 216
Kojberg, H. 751
Koh, H. 328
Köhler M. 623, 650, 786
Kohlmann, A. 676, 690
Kohrs, C. 743
Kokornaczyk, A. 160
Kolarova, J. 200
Kolbe, K. 452
Kolben, T. 893
Kolberg, G. 550, 559, 774
Kölbl, O. 387, 410, 506
Kolinsky, M. 676
Koll, F. 1023
Kollmannsberger, C. 993
Kollmeier, J. 190, 635, 934
Komatsubara, K. 884
Konczalla, L. 551
Kong, A. 900
König, A. 704
König, M.-T. 999
König, V. 165
Königsrainer, A. 538, 758
Konsgen-Mustea, D. 1029
Konsortium, FARKOR. 264
Konstantinov, S. 1033
Konzelmann, I. 64, 65
Kooymann, J. 441
Kopetz, S. 608
Kopka, K. 216
Köppel, M. 730, 996
Koppelle, A. 194
Köppler, H. 184
Kordes, U. 41
Korinetska, N. 438
Kornmann, M. 897
Kortüm, B. 799
Kosiorek, H. 1052
Kostin, A. 851, 976
Koutzamanidis, R. 889
Kowald, B. 155
Kowalski, C. 470, 798
Kowalski, D. 659
Kozak, T. 183
Krahl, R. 529
Krämer, H. 1007
Krämer, N. 756
Kratochwil, C. 216
Krause, J. 551
Krause, K. 789
Krause, S. 215
Krause, Stefan W. 420
Krauss, J. 37
Kraywinkel, K. 369, 451, 617, 671
Krebs, Matthew G. 402, 992
Krebs, S. 208
Kreipe, Hans H. 563
Kreißl, M. 301
Kremeike, K. 56
Kremer, A. E. 931
Kretz, T. 463
Kretzschmar, A. 324, 452, 476
Kreutzfeldt, S. 112
Kreyer, R. 512, 515
Kriegmair, M. 610, 634
Kriegmair, Maximilian C. 546
Kriegsmann, K. 115
Kriegsmann, M. 115
Krings, A. 645
Krippgans, S. 475
Kristiansen, G. 194, 899
Kroeger, N. 956
Kröger, B. 605, 682
Kröger, N. 640
Krolo, F. 304
Kron, F. 421, 1022
Kropp, P. 813
Kröz, M. 311, 680
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Inhalt
2018
Index
2018
Krücken, I. 373
Krug, D. 170
Krug, S. 589
Krug, U. 445
Kruger, S. 761
Kruger, C. 972
Krüger, T. 317
Kruggel, L. 254
Krumbach, J. 294, 313
Krummradt, F. 115
Kryachok, I. 183
Ku, Nora C. 282
Kubasch, Anne S. 781
Kübler, Hubert R. 727, 1023
Kubota, Y. 788
Kuchenbaecker, K. 585
Kuczyk, Markus A. 899
Kühlmann, B. 114
Kuhlmann, J. D. 950
Kuhn, C. 801
Kühn, R. 334
Kuhns, M. 444
Kulik, A. 766
Kulkrani, Harshad R. 25
Kullmann, F. 404, 756
Kummar, S. 274
Kümmerl, L. 873
Kunz, M.-A. 999
Kunz, C. 640
KUNZMANN, B. 93
Kunzmann, V. 404
Kuon, J. 409, 520
Kurata, T. 579
Kurbacher, A. T. 552, 559, 774
Kurbacher, C. 303
Kurbacher, Christian M. 550, 552, 559, 774
Kurbacher, Jutta A. 550, 552, 559, 774
Kuriki, H. 884
Kurreck, A. 348
Kurz, D. 113
Kurz, T. 766
Kurze, I. 155
Kusch, M. 208
Kuss, I. 249
Kussmaul, J. 891
Kuziora, M. 644
Kwang Chae, Y. 586
L
La Rosée, P. 647, 963
Laack, H.-E. 934
Laban, S. 200, 287, 397, 474
Lackmann, K. 1047
Ladd, Mark E. 519
Ladigan S. 901
Laetsch, Theodore W. 274
Lafond, C. 1053
Lahner, H. 703
Lakowa, N. 82
Lammert, A. 194
Lam, S. 886
Lamy, F-X. 1019
Landendinger, M. 889
Lang, K. 697
Lang, Sven A. 403, 627, 631, 758, 840
Lange, F. 383
Lange, T. 420, 744
Langer T. 623, 650
Länger, F. 563, 782
Langheinrich, M. 389, 820
Längler, A. 494, 743
Langner, I. 88
Lapa, C. 157
Lashgari, M. 686
Lassen, U. 274
Lassmann, I. 144
Lau, A. 599
Laubenstein, Hans-P. 184
Laus, G. 659
Lawson McLean, A. 584
Layer, M. 793
Le Berre, Marie-A. 249
le Coutre, P. 420
Le Rhun, E. 168
Leal, T. 886
Lebioda, A. 57, 448
leblanc, D. 545
Lebrec, N. 545
Lederer, B. 142, 636
Lee, A. 585
Lee, H. 804
Lee, J.-S. 886
Lee, Jae H. 183
Lee, Ji Y. 372
Lee, Jung-H. 55
Lee, K.H. 581, 644
Lee, Ki H. 579, 875
Le-Guennec, S. 482
Lehmann, H. 405
Lehmann, N. 45
Lehnhardt, M. 307, 331, 388
Leibbrand, B. 346
Leiblein, S. 819
Leinert, E. 814
Leleu, X. 482, 804
Lemke, C. 492
Lempert, Lilli M. 779
Lempfert, S. 797
Lennartz, F. 514
Lenz, C. 363, 449
Leppin, N. 921
Leopold, C. 980
Lesakova, K. 200
Lesyuk, W. 873
Letsch, A. 143, 304, 428
Leuchter, M. 569
Lewis, I. 226
Lewis, J. 853
Leyvraz, S. 274, 282
LI, D. 882, 976
Li, F. 226
LI, J. 963
LI, s. 1000
Li, Y. 172
Liang, W. 183
Liang, Y. 893
Liebeskind, Juliane M. 853
Liersch, R. 270, 272, 472
Lihou, C. 916
Lim, H. 882
Lin, Chen-Y. 788
Lin, H.M. 875
LIN, LILI. 801
Lin, Meng C. 607
Linardou, H. 1000
Lindig, A. 457, 465, 573
Lindner, L. 673
Lindner, R. 56
Lindörfer, D. 264
Lindviksmoen Astrup, G. 570
Link, Karl-H. 897
Link, T. 588, 636
Linnebacher, M. 569, 630
Lipke, J. 214, 392
Lippert, H. 512, 515, 516, 517
Litcheld, L. 167
Litzow, M. 1052
Liu, F. 644
Liu, J. 882
Liu, L. 251
Liu, S. V. 886
Liu, Z. 106
Llombart-Cussac, A. 167, 328
Llorente, M. 963
Lmpert, L. 779
Locker, Gershon Y. 822
Löhr, M. 433, 789
Loibl, S. 142, 588, 629, 636, 683, 694
Loidl, W. 463
Longerich, T. 112
Loong, Herbert H.F. 402
Lopez-Gitlitz, A. 372
Lopez-Rios, F. 295
Loquai, C. 889
Lorch, A. 463
Lordick, F. 218, 452, 476
Lorenz, A. 254
Lorenzen, S. 199, 218
Lorinser, V. 1047
Lorenzini, T. 1040
Loriot, Y. 295, 488
Losem, C. 392, 394
Losonczy, G. 399
Lösse, V. 682
Loupakis, F. 608
Lower, M. 900
Lübbe, K. 142, 636
Luber, B. 452, 476
Lübke, J. 742
Lück, Hans-J. 523, 691
Lücke, E. 301
Ludescher, M. 757
Luft, A. 581, 644
Lüftner, D. 270, 272
Lugnier, C. 533
Luka, B. 187
Lukic, S. 722
Lunning, M. 976
Lunger, L. 980, 1023
Luo, Z. 715
Lupp, A. 535
Lupinacci, L. 1008
Lurje, I. 763
Lutschkin, J. 184
Luu, A. 646, 854
Lux, Michael P. 421, 485, 913
LWBC Steering Group, NCRI. 226
Lyros, O. 759, 800
Lysak, D. 183
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 257
Inhalt
2018
Index
2018
M
Maas, V. 294, 313, 682
Maasberg, S. 703
Maatouk, I. 26, 71, 375
Macarulla Mercade, T. 822
Macé, S. 482
Machetanz, K. 965
Machova Polakova, K. 744
Magerhans, A. 528
Maghnouj, A 901
Magios, N. 409
Maharry, K. 608
Mahlberg, R. 194
Mahler, C. 642
Mahner, S. 262, 461, 493, 523, 893
Maichl, Daniela S. 188
Maier, D. 452, 476
Maier, J. 744
Maintz, C. 394
Mainwaring, Paul N. 372
Mairinger, E. 190, 604, 606, 635
Mairinger, Fabian D. 190, 604, 606, 635
Mairinger, T. 190, 635
Maisch, P. 1023
Majchrzak-Stiller, B. 455
Majem, M. 607, 659, 997
Mak, G. 652
Maktabi, M. 802
Malek, N. 400, 454
Malfertheiner, P. 918
Malila, N. 568
Maloney, D. 976
Malki, K. 45
Malte, E. 672
Maly, R. 759
Mamlouk, S. 334
Manapov, F. 555
Mancuso, K. 302
Mangana, J. 816
Manger, B. 889
Mangeshkar, M. 174
Manisha, J. 853
Mann, J. 623, 650
Manseld, A. S. 886
Mansmann, U. 264
Mantey, R. 288
Manz, K. 420
Mänz, M. 463, 958
Manzini, V. 528
Marienfeld, R. 287
Marinis, F.D. 884
Markby, D.W. 117
Marmé, F. 211, 523, 683, 629, 691
Marmol, D. 659
Maroto, J. 1037
Marotti, M. 659
Marquard, S. 605
Marquis, A. 645
Marschner, N. 254, 270, 272, 391, 392,
393, 394, 395, 405, 426
Marstaller, K. 962
Marten-Mittag, B. 144
Martens, U. 236, 260, 404
Martin, B. 462
Martin, L. 1053
Martin-Diener, E. 64, 65
Martus, P. 642
Maruschke, L. 739
Marx, A. 755
Mascarenhas, L. 274
Maschmeyer, G. 529
Masini, C. 295
Masuda, N. 328
Mateo, J. 690
Mathes, S. 845
Mathis, K. 730
Matschos, S. 569
Matsubara, N. 676
Matthes, H. 680, 894
Matyschik, L. 208
Maurer, J. 417
Maurer, M. 323
Mäurer, M. 170, 675
Mauz, Paul-S. 259
Mayer, A. 666
Mayr, D. 262, 461, 493, 893
Mccleland, M. 884, 886
McDermott, David F. 132
McDermott, R. 274
McGuinness, D. 822
McHenry, B. 132
McHenry, M. B. 323
McKeown, A. 607
McLaurin, K. 232
Medenwald, D. 414, 441, 503, 544, 583, 998
Medinger, T. 392
Medl, M. 310
Meeks, Joshua J. 727
Meessen, S. 443
Meert, C. 842
Meert, L. 194
Meggendorfer, M. 742
Mehanna, H. 900
Mehdorn, Anne-S. 611
Mehdorn, M. 800
Mehl, A. 311
Mehra, N. 676, 690
Mehta, A. 976
Meidenbauer, N. 889
Meier, F. 320
Meier, S. 235
Meier, W. 523
Meierjürgen, R. 182
Meier-Stiegen, F. 215, 628, 849
Meiler, J. 463
Meindl, A. 585
Meinlschmidt, G. 842
Meiß, F. 320
Meißner, C. 44
Meissner, M. 654, 823
Meister, M. 374, 409
Meker, T. 171
Melisi, D. 916
Melzer, A. 802
Mellado, B. 1037
Menck, K. 449, 459
Mentzer, D. 889
Menzel, H. 722
Menzel, M. 403, 631, 840
Menzler, S. 382
Merk, D. 625
Merkel, S. 130, 131, 341
Merle, P. 882
Merseburger, Axel S. 295
Mertens, I. 793
Mertins, P. 794
Mesa, R. 1052
Merzenich, H. 501
Messinger, D. 1019
Mesia, R. 1053
Messmann, H. 382
Metter, K. 382
Metz, M. 458, 463
Metzeler, K. 445, 461, 687, 702
Metzeler, Klaus H. 701
Metzler, M. 623, 650
Metzenmacher, M. 395, 464
Metzgeroth, G. 742, 755, 781
Metzner, B. 640
Meyer, F. 220, 221, 408, 512,
515, 516, 517, 614, 827, 836
Meyer, G. 692, 706
Meyer, R. 539
Meyer, T. 174, 235
Meyer zum Büschenfelde, C. 411
Michael, Q. 199
Micheel, B. 569
Michel, C. 1053
Michel, S. 776
Michl, M. 756
Michl, P. 503, 589, 612, 618
Mies, A. 781
Mihaljevic, A. L. 971
Mika, S. 985
Mikolajczyk, R. 544, 583
Miller-Phillips, L. 687
Milwee, S. 171
Minarik, J. 482
Mischke, M. 830
Mittelbronn, M. 386
Mladenovic, M. 543
Möbus, V. 142, 588, 636, 683
Mocci, S. 884
Modest, Dominik P. 348, 756
Mogler, C. 475
Mohamed, Ateesha F. 249
Möhler, M. 756
Mohnike, K. 614
Mohr, J. 111
Mohr, P. 320
Mok, T. 886, 1009
Mölle, U. 570
Möllenkötte, I. 255
Möller, Y. 400
Mollon, P. 172, 174
Momberg, A. 539
Monga, M. 488
Monroy Ordonez, Elsa B. 187
Morakis, P. 322
Moreau, P. 482
Morgan, M. 337, 720
Morise, M. 884
Moro-Sibilot, D. 242
Motzer, Robert J. 132, 323, 993
Mousavi, Seyed M. 64, 65
Mph, L.H. 889
Muallem, Mustafa Z. 576
Muche, R. 382
Mücke, Victoria T. 266
Mügge, Lars-O. 647
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Inhalt
2018
Index
2018
Muhomedyarova, A. 833
Mukhopadhyay, P. 581
Mukhopadhyay, S. 488
Muley, T. 374, 409
Mulla, S. 882
Müller, A. 119
Müller, B. 252
Müller, C. 150
Muller, J. 996
Müller, L. 185, 391, 463, 533
Müller, S. 600
Müller, V. 142, 215, 629, 845
Müller-Decker, K. 149
Müller-Huesmann, H. 259, 324, 472
Müller-Nordhorn, J. 314
Müller-Tidow, C. 115
Mullins, C. 569, 630
Mumm, F. 251, 445
Munir, T. 236
Munugala, V. 236
Munshi, N. 956
Munzel, T. 501
Munugala V. 236
Muradyan, A. 851
Murakami, S. 579
Murphy, A. 916
Mustea, A. 576, 684, 1029
Musuraca, G. 183
N
Nabieva, N. 994
Nadal, E. 242
Nadalin, S. 538
Nagelschmidt, K. 921
Nahnsen, S. 514
Naini, V. 488
Nakagawa, K. 242
Nanda, S. 274, 282
Naskou, J. 849
Nassiri, F. 965
Nathan, F. E. 1008
Naumann, N. 742
Necchi, A. 488
Neeb, C. 891
Neef, U. 303
Nee, Hannes P. 840
Negrier, S 1037
Nekljudova, V. 142, 588, 629, 636, 694
Nelep, C. 582
Nestle, U. 261, 738
Neu, M. A. 501, 941
Neu, M. 45
Neubauer, H. 582, 628, 757, 766, 849
Neuberger, P. 793
Neugebauer, S. 797
Neumann, J. 555
Neumann, M. 514
Neumann, Ulf P. 689
Neumuth, T. 802
Neunhöer, T. 683
Neurath, M. F. 931
Neven, P. 167, 328
Nguemgo-Kouam, P. 686
Ni, Q. 875
Nickel, F. 889
Nickel, N. 255
Nieberler, M. 475
Niederacher, D. 582, 585, 598, 628,
766, 849
Niederberger, U. 986
Niedermann, G. 738
Niederwieser, C. 529
Niederwieser, D. 420, 482, 529, 744,
747, 754
Niels, T. 960, 1043
Niemeyer, C. 623, 650
Niesen, J. 972
Nietert, M. 704, 903
Nieth, R. 34
Nishio, M. 242, 886
Nishiyama, H. 727
Nitsch, T. 434
Noack, S. 669
Noeding, H. 459
Nolte, F. 755
Nolting, J. 148
Nöpel-Dünnebacke, S. 252, 533
Noseir, S. 901
Nordhausen, T. 692
Norman, K. 379
Nöthling, C. 310
Novello, S. 242, 659
Novick, S. 956
Nowak, D. 755
Nowak, V. 755
Nowotny, R. 759
Nusch, A. 254, 393
O
Oberhoer, R. 396
Oberhoer-Fritz, R. 968
Obertacke, U. 708
Obländer, J. 755
O’byrne, K. 1008
Odemar, F. 382
Odom, D. 249
Oechsle, K. 143
Oei, Shiao L. 680
Oertel, M. 170
Oringa, R. 263
Ogrodnik, Simon J. 374
Oh, Do-Y. 822, 916
Oh Park, J. 822
Ohlig, H. 635
Okada, M. 788
Okamoto, I. 607
Olbrich, C. 1027, 1028
Oles, M. 112
Olmos, D. 372, 690
Önur, Ö. 400
Oosting, S. 1037
Oppelt, K. 638
Oppermann, H. 913
O‘Reilly, Eileen M. 822
Orfao, A. 742
Ori, A. 111
Orlandi, F. 886
Ormanns, S. 761
Orth, M. 555
Ortiz-Brüchle, N. 763
Ortmann, O. 153, 360, 378, 470, 478,
485, 487, 504, 540, 657,
835, 843, 848, 913
Osborne, K. 208
Oschwald, V. 294, 313
Osen, W. 263
Oskay-Özcelik, G. 303, 684
Ostalecki, C. 55
Ostermann, H. 591
Ostermann, T. 311
Ostheimer, C. 544, 583
Otremba, B. 495
Ott, G. 769
Otten, L. 379
Otten, S. 294, 313, 682
Otto, H. 45
Otto, R. 220, 221, 512,
515, 516, 517
Otto, S. 776, 819
Otto, W. 383
Ou, S-H. 1009
Oudard, S. 372
Overbeck, T. 402
Overkamp, F. 1091
Ozguroglu, M. 579
Özgüroğlu, M. 399, 676, 884
Öztürk, A. 659
P
Pabst, U. 723
Pachmann, K. 675
Pachmann, U. 675
Pachmayr, E. 794
Padua, C. 676
Paech, D. 519
Paelecke, A. 250
Paepke, D. 845
Paepke, S. 262
Pagel, John M. 236
Pal, S. 993
Pallasch, Christian P. 255
Pallisgaard, N. 744
Palm, F. 544
Palme, I. 755
Palmer, J. 1052
Palomba, M. L. 976
Palumbo, A. 804
Panic, A. 1037
Panzica, M. 782
Papadimitrakopoulou, V. 644
Papavasiliou, N. F. 933
Papathemelis, T. 478, 485, 913
Pape, Ulrich-F. 703
Paret, C. 45
Park, K. 242
Park, Se H. 488
Park, S. 781
Park-Simon, Tjoung-W. 523
Parmentier, S. 769
Parsch, W. 693
Patel, P. 183, 236
Patil, D. 731
Paul, A. 898, 985
Pauer, A. 913
Pauligk, C. 218
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 259
Inhalt
2018
Index
2018
Paulson, A. 916
Paulussen, M. 203
Pauly, N. 265
Pavel, M. 889
Pavel, P. 115
Paz-Ares, L. 399, 991, 992,
1000, 1008
Paz-Ares, Luis G. 579
Pech, M. 832
Pecori, R. 933
Peeck, M. 903
Peglow, S. 827
Pelageev, Dmitry N. 326, 530
Pellan, M. 448
Pelzel, D. 317
Pelzer, U. 404
Peng, L. 352
Perez, D. 551
Perez-Hernandez, D. 853
Perkhofer, L. 382
Perkins, C. 742
Perol, M. 1009
Perner, F. 111
Perrot, V. 619
Pession, U. 223
Peter, N. 529
Peters, B. 296
Peters, C. 396, 968
Peters, S. 644, 1008, 1009
Petersen, C. 836
Petersen, M. 827
Petridis, F. 235
Petrocca, F. 956
Petzka, A. 82
Pfa, H. 575
Pfannstiel, C. 383, 980
Pfarr, N. 475
Pfau, G. 408
Pfeifer, D. 742
Pfeier, N. 501
Pfeilschifter, J. 467
Pfender, K. 801
Prrmann, M. 420, 486
Psterer, J. 523
Pfohl, U. 334, 362
Pföhler, C. 320
Phan, S. 886
Piccioni, F. 625
Pichler, T. 428
Pienaar, A. 350
Pieper, A. 388
Pieper, M. 605
Pigorsch, S. 194
Pilgrim, K. 235
Pillai, R. 1000
Pink, D. 218, 673
Pinter, A. 816
Piso, P. 758, 830
Pisotska, L. 238
Pitcher, B. 991, 992, 948
Pitkäniemi, J. 568
Pivot, X. 328
Pizon, M. 675
Planchard, D. 579
Plath, M. 570
Platt, T. 519
Platten, M. 86
Platzbecker, U. 747, 754, 776,
781, 819
Pless, M. 842
plett, H. 265
Plinkert, P. 37
Pluta, A. 183
Poddubskaya, E. 1000
Pohl-Rescigno, E. 142, 162, 197, 585
Pointner, R. 776
Polasik, A. 215
Pölcher, M. 493
Poltoratskiy, A. 399
Polzer, B. 628
Ponce, S. 399
Ponce Aix, S. 242
Popat, S. 875
Popp, O. 794
Porubsky, S. 546, 610, 634
Poso, A. 386
Pottho, K. 270, 272,
276, 458
Powerski, Maciej J. 614
Powles, T. 132, 295, 323, 727
Prader, S. 265
Prager, G. 608
Prall, F. 569
Pralong, A. 56
Prantl, L. 114
Preidl, R. 600
Preisler, M. 304
Prenninger, S. 214
Pretzell, I. 574
Preuß, C. 464
Priesch-Grzeszkowiak, B. 686
Priese, J. 446
Prince, H. M. 482
Prinz, M. 86
Pritzkuleit, R. 122, 289, 792, 803
Probst, S. 218
Prochaska, J. 501
Prokop, A. 294, 313, 682
Pryztal, J. 514
Przystal, Justyna M. 438
Ptok, H. 220, 512, 515,
516, 517
Puig, N. 804
Pukrop, T. 903
Pulewka, K. 813
Puntigam, L. 474
Puntscher, S. 543
Purev, E. 976
Pusch, S. 86
Q
Qin, S. 882
Quah, C. 183
Quang, B.V. 659
Quietzsch, D. 703
R
Raab, M. 956
Rabe, A. 695
Rachow, T. 554
Raddatz, V. 837
Radhakrishnan, H. 799
Radke, J. 606, 635
Radlanski, K. 41, 296
Radziwill, R. 198
Rayan, Mohamed-R. 463
Rahbari, Nuh N. 58, 169, 981
Rahn, S. 67
Raimundez, E. 476
Raineteau, O. 514
Raje, N. 956
Rajkumar, V. 482
Raju, A. 804
Ramalingam, Suresh S. 411, 607, 1008
Rajaraman, S. 514
Ramdani, H. 594
Randazzo, M. 64, 65
Ranft, A. 203
Rapp, M. 655, 658, 660
Rastogi, P. 694
Rath, Hilke M. 143
Rathke, H. 216
Ratzel, E. 574
Ratzisberger, A. 387, 410
Rau, B. 452, 476, 794
Rau, J. 523
Rau, S. 187
Rauchfuss, F. 861
Rauh, J. 272, 395
Rausch, C. 702
Rauscher, B. 149
Rauscher, I. 199
Ray-Coquard, I. 691
Ready, N. 1000
Reber, J. 466
Rechenmacher, M. 835
Reck, M. 242, 297, 374, 393,
659, 886, 934, 1008
Regber, L. 238
Regenbrecht, C. 334, 362
Regnery, S. 519
Rehm, A. 467
Reißfelder, C. 981
Reich, F. 934
Reichardt, P. 218, 673
Reichelt, R. 741
Reichert, D. 391
Reif, M. 311
Reifenrath, Kolja F. B. 529
Reimer, N. 536
Reimer, T. 683
Reinacher-Schick, A. C. 194, 533, 822
Reinert, S. 268
Reinhardt, D. 623, 650, 1016
Reinhardt, F. 628, 849
Reinhart, S. 112
Reinhold, T. 894
Reinisch, M. 683
Reinmuth, N. 399, 411, 484,
581, 607, 644, 884, 886
Reis, D. 743
Reis, H. 464, 898, 985
Reiser, H. 769
Reiser, M. 214, 393
Reissfelder, C. 58, 169
Reiter, A. 742
Remane, Y. 819
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Oncol Res Treat 2020;43(suppl 1):1–265 Author Index260
Inhalt
2018
Index
2018
Remiro Azocar, A. 172
Rendenbach, B. 184, 185
Reni, M. 822
Renner, A. 28
Renner, S. 691
Renovanz, M. 400, 699, 965
Rentschler, J. 123
Renziehausen, A. 226
Retz, M. 980, 1023, 1037
Reu, S. 555
Reuss-Borst, M. 321, 338
Reuter, C. 335, 337, 720
Rezai, M. 984
Rhiem, K. 142, 197, 265, 588, 636,
694, 814, 1032
Ricard, I. 251
Ricci, F. 330
Ricciardi, E. 265
Richardson, P. 482
Richter, G. 1048
Richter, J. 71
Richter, R. 684
Richter, S. 673
Richters, L. 162
Ricke, J. 614, 836
Ridwelski, K. 44
Rieckmann, N. 314
Rief, H. 732
Riehl, T. 995
Rief, W. 921
Rieken, S. 37, 263, 409, 519
Riera, J. 452, 476
Riera-Knorrenschild, J. 276
Ries, Carola H. 438
Ries, J. 595, 600
Riese, C. 251, 771
Rieth, A. 448
Riethdorf, S. 215
Rifkin, R. 804
Rijavec, E. 1000
Rimassa, L. 117
Rindtor, N. 149
Rinecker, J. 475
Rini, Brian I. 132, 323, 993
Rinke, A. 703
Rinke, J. 486
Rischke, Hans-C. 261
Ristau, P. 605
Ritter, A. 310, 774
Ritterbusch, U. 560
Rittmeyer, A. 394, 934
Ritzel, C. 900
Rivandi, M. 582
Rizvi, N. 581, 644
Rizzu, P. 514
Robert, P. 853
Robinson, A. L. 941
Robinson, A. 941
Roca Ripoll, B. 504
Rochau, U. 543
Rochlitz, C. 842
Rödel, C 1023
Röder, C. 67
Röder, I. 288, 641
Rodrigues Recchia, D. 311
Rodríguez-Cid, J. 132
Rody, A. 637, 845
roeder, christia. 678
Roengvoraphoj, O. 555
Roeper, J. 181, 464
Roesch, R. 475
Rogge, A. 494
Roggendorf, S. 599, 612
Roggia, C. 400, 625
Roghmann, F. 546, 610, 634
Rogmans, G. 458
Rohde, V. 903
Rohlng, T. 530
Rohlmann, F. 382
Rohrmann, S. 64, 65
Rohrmoser, A. 304, 428
Rol, J. 630
Rolfo, C. 586, 991
Rolinger, J. 538
Romanus, D. 804
Rom-Jurek, Eva-M. 540
Roquette, K. 126
Rosell, R. 1009
Rosenberger, F. 732
Rosenwald, A. 769, 834
Rossig, C. 623, 650
Rosery, V. K. 898, 985
Rossig C. 623, 650
Roth, W. 661
Rothe, V. 1019
Rothenberg-Thurley, M. 445, 702
Rotmann, André R. 667, 674
Rottey, S. 1037
Röttger, M. 815
Rottmann, M. 491, 493
Roubaud, G. 676
Rouse, R. A. 931
Rouyer. M 1019
Rücker, G. 310
Rückert, A. 411
Ruckhäberle, E. 849
Rüddel, U. 156
Rudlowski, C. 552, 847
Rudolph, L. 235, 335
Rudzinski, Erin R. 274
Ruessel, J. 503
Ruf, J. 261
Rühle, A. 787
Ruhm, K. 400
Rukazenkov, Y. 411
Ruland, J. 475
Rummeny, E. 899
Rummel, M. 963
Runkel, M. 627
Runnebaum, Ingo B. 497, 669, 691,
837, 1035
Ruppert, L. 486
Ruppert, M. 151
Ruppert, R. 367
Ruschpler, E. 819
Russo, A. 45
Rüthrich, Maria M. 647
Rutkowski, S. 623, 650
Rutkowski, W. 433
Ryabov, V. 755
Ryoo, B.-Y. 117
S
Saad, F. 372, 676, 690
Saada-Bouzid, E. 1053
Saba, G. 448
Sabel, M. 655, 658, 660
Sachse, C. 362, 799
Sachse, M. 816
Sack, U. 853
Sackmann, S. 181
Sadjadian, P. 395, 1051
Saggese, M. 607
Saglio, G. 744
Sahai, V. 916
Sahin, G. 162
Sahin, U. 900
Sahlmann, J. 270, 272, 393, 394, 395
Sakai, H. 1008
Salat, C. 636
Salazar, R. 1016
Salchow, J. 623, 650
Salles, G. 236
Salmon, M. 744
Sanchez, H. 124
Sander, A. 623, 650
Sander A. 623, 650
Sander, S. 112, 897
Sandhu, S. 676, 690
Sandor, V. 608
Sänger, J. 535
Sankowski, R. 86
San-Miguel, J. 482
Santamaria, J. 543
Santiago-Walker, A. 488, 610
Sapena, R. 781
Sarapohja, T. 249
Saribekyan, E. 817
Sartor, O. 690
Satzger, I. 563
Sauer, S. 115
Sauerland, Maria C. 445
Saura, C. 119
Sauter, A. 1023
Saußele, S. 420
Savvatakis, K. 898
Sayer, H. 529
Schad, F. 519, 680, 894
Schadendorf, D. 320
Schäfer, H. 194
Schäfer, N. 499
Schäfer, S. 339
Schäfer, T. 338
Schäfert, R. 842
Schäeler, N. 268, 431, 699
Schafhausen, P. 1053
Schafmayer, C. 678
Schaich, M. 769
Schallehn, M. 1047
Schaper, T. 984
Scharl, A. 478, 485, 913
Scharl, S. 466, 478, 485, 913
Schatz, S. 594
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 261
Inhalt
2018
Index
2018
Schaub, L. 672
Schawan, S. 255
Scheer, K. 560
Scheerer, B. 124
Scheich, S. 266
Scheid, C. 956
Scheithauer, W. 756
Schellerer, V. 130, 131, 341, 502
Schem, C. 119, 629
Schenk, R. 506
Schenk, T. 769, 834
Scherf, N. 641
Scherpereel, A. 886
Scheungraber, C. 497
Scheuring, U. 581, 644
Schierer, S. 55
Schierle, K. 452, 476
Schierling, C. 431
Schildhaus, Hans-U. 704
Schildmann, J. 743
Schiller, K. 1023
Schilling, B. 816
Schilling, J. 303
Schilliro, A. 260
Schimek-Jasch, T. 738
Schimmöller, L. 899
Schindele, D. 832
Schindlbeck, C. 262
Schinköthe, T. 771
Schirmacher, P. 672
Schirmer, D. 1048
Schirmer, M. 704
Schittenhelm, J. 386, 400, 438, 965
Schjesvold, F. 482
Schleif, D. 1016
Schlecht, J. 501, 941
Schlemmer, Heinz-P. 519, 899
Schlenk, Richard F. 781
Schlesinger-Raab, A. 361, 367
Schlesner, M. 374
Schleyer, E. 776
Schlichtig, K. 567
Schlienger, K. 822
Schlitt, H. 830
Schlüter, K. 619
Schlüter, N. 187
Schmalfeldt, B. 523, 691, 845
Schmatloch, S. 629, 683
Schmeling, B. 793
Schmell, S. 288
Schmid, Hans-P. 64, 65
Schmid, Kurt W. 190, 464, 604,
606, 635
Schmid, R. 199
Schmidt, B. 963
Schmid, S. 1023
Schmidinger, M. 993
Schmidt, E. 682
Schmidt, G. 150
Schmidt, H. 441, 503, 599, 612,
618, 692, 706
Schmidt, L. 256
Schmidt, M. 138, 531, 585, 683,
941, 1007, 1016
Schmidt, S. 188
Schmidt, V. 529
Schmidt-Wolf, I. 489
Schmitt, A. 115
Schmitt, Clemens A. 524
Schmitt, N. 755
Schmittnaegel, M. 438
Schmitz, K. 730
Schmitz, M. 446, 497, 1035
Schmitz, Rosa L. 589
Schmunz, J. 124
Schmutzler, R. 197, 636, 1032
Schmutzler, Rita K. 142, 162, 265,
585, 814
Schnabel, J. 547
Schneeweiss, A. 142, 215, 588,
629, 636, 694,
Schneider, A. 432, 501, 597
Schneider, K. 382
Schneider, Marc A. 374
Schneider, N. 316, 539
Schneider, Stefan W. 320
Schneider, S. 265, 702
Schneider, U. 763
Schnelzer, A. 262, 493, 691
Schnetzke, U. 554
Schnitzler, T. 763
Schnöder, T. 111
Schnöder, Tina M. 613
Schober, S. 1048
Schochter, F. 215
Schoeder, V. 827
Schöhl, M. 448
Scholl, C. 112, 382, 613
Scholl, I. 457, 465, 573, 587
Scholl, S. 529, 554
Scholz, N. 220
Schömel, F. 363
Schönfeld, V. 645
Schöps, W. 155
Schorer, H. 367
Schostak, M. 324, 463, 832
Schott, A. 552, 559
Schott, D. 675
Schott, S. 814
Schranz, M. 235
Schreiber, J. 301
Schrenk, K.G. 156
Schröder, Jan C. 329
Schröder, K. 605
Schröder, L. 847
Schröder, W. 523
Schrodi, S. 262
Schroeder, M. 912
Schrors, B. 900
Schröter, P. 263
Schubert-Fritschle, G. 300, 361, 491, 493
Schubotz, B. 547
Schuch, G. 632
Schuler, G. 55
Schuler, M. 464, 489, 898, 985
Schuler, P. 200
Schuler, Patrick J. 287, 329, 397, 474
Schüler-Toprak, S. 360
Schüller, E. 1022
Schüller, U. 625, 972
Schulte, C. 472
Schultheiss, M. 739
Schultze-Seemann, W. 324
Schulwitz, H. 144
Schulz, A. 501
Schulz, H. 185, 350, 353, 355,
426, 472, 547
Schweithauer, W. 1016
Schulz, J. 747, 754
Schulz, M. 449
Schulz, S. 535
Schulze, S. 700
Schumacher, M. 499
Schumann, C. 472, 484
Schuster, S. 623, 650, 731
Schütt, P. 463
Schütte, K. 489
Schütte, W. 484
Schuuring, E. 594
Schwaab, J. 742
Schwaiger, M. 199
Schwarz, S. 638, 688
Schwarze, N. 809
Schweiger, C. 615
Schweitzer, C. 550, 559, 774
Schwettmann, L. 122
Schwind, S. 747, 754
Scialdone, A. 701
Scott, M. 581
Sebastian, M. 297, 393, 394, 395, 472
Sebens, S. 67, 678
Secci, R. 475
Seckler, A.-M. 962
Seefried, L. 157
Seeling, S. 605
Sehgal, A. 976
Sehner, S. 25
Sehouli, J. 211, 523, 576, 684, 691
Seidel, N. 462, 609
Seidensticker, M. 614
Seifart, U. 165
Seifert, U. 111
Seiler, S. 588, 683, 694
Seither, F. 683
Seitz, A. 1023
Seitz, S. 504, 540, 835, 843, 848
Selig, L. 124
Semrau, S. 130
Semsek, D. 458
Sen, S. 117
Senan, S. 652
Senkal, M. 533
Sens-Albert, C. 755
Seppä, K. 568
Serve, H. 266
Seto, T. 242
Settmacher, U. 859, 860, 861
Seuerlein, T. 382
Shang-Yi Huan, J. 482
Shao, H. 882
Sharman, J. 236, 963
Shaw, Alice T. 402, 992, 995, 1009
Shehu, E. 503, 599
Shih, Jin-Y. 242
Shire, N. 399, 652
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Oncol Res Treat 2020;43(suppl 1):1–265 Author Index262
Inhalt
2018
Index
2018
Shirokich, I. 817
Shore, N. 676, 690
Shore, Neal D. 249
Shoumariyeh, K. 742
Si, H. 644
Sianidou, M. 201
Sibert, Nora T. 470, 798
Siebert, S. 1043
Siddiqi, T. 976
Siebert, U. 264, 543
Siebler, J. 931
Siefker-Radtke, A. 488
Siegle, A. 125
Siegler, G. 404, 452, 476, 533
Siena, S. 402, 586, 948, 992,
Siener, R. 899
Siesling, S. 748, 751
Sieverding, M. 256
Sigal, D. 586
Sikic, D. 383, 546, 610, 634
Silke, H. 269
Silvestri, A. 334
Šimkovič, M. 183
Simm, A. 706
Simmons, B. 586, 948, 991,
992, 995
Simmons, Brian P. 402
Simon, Steen T. 56
Singer, S. 235, 570
Singh, M. 57, 448
Siniatchkin, M. 986
Sinn, B. 683
Sipos, B. 703
Sire, C. 1053
Sirokay, J. 499
Sitskaia, X. 722
Sitte, M. 459
Siveke, J. 199, 404, 898, 985
Skacel, T. 804
Skarbnik, Alan P. 236
Skardelly, M. 386, 965
Slack, J. 1052
Sledge, George W. 167, 328
Slotta-Huspenina, J. 199
Small, Eric J. 372
Smith, A. 372
Smith, Matthew R. 249, 372
Smoljanovic, V. 1009
Snapir, A. 249
Sobrero, A. 1016
Sockel, K. 781
Soerensen, L. 298
Sogorski, A. 331
Sohal, D. 282
Sohn, Joo H. 167, 328
Sökler, M. 218
Solbach, C. 588, 694
Soliman, H. 167
Söling, U. 254
Solomayer, Erich-F. 150
Solomon, S. 976
Solovey, M. 701
Sommer, Ann-K. 684
Sommer, L. 641
Sorensen, P. 1048
Sotlar, K. 742
Soverini, S. 744
Speiser, D. 814, 891, 899, 1028
Sperlich, B. 157
Sperling, C. 288, 641
Sperr, W. R. 742
Spicka, I. 482
Spiekermann, K. 445, 702
Spigel, D. 884
Spira, A. 875
Spix, C. 941
Spohn, M. 625
Sporleder, J. 200
Sprave, T. 732
Spring, L. 393, 394, 395
Springfeld, C. 948
Sprute, K. 216
Srinivasan, A. 731
Sroczynski, G. 264, 543
Staehelin, K. 64
Staehler, M. 391
Staehlin, K. 65
Stahl, M. 218, 608
Stahler, A. 756
Staib, P. 463
Stamm, N. 757
Stang, A. 541
Stange, K. 782
Stangl, G. 441, 599
Starke, M. 1016
Statsenko, G. 399
Stäuber, A. 350, 353, 355, 547
Stauch, T. 302
Staufenberg, Anna-R. 200
Steckelberg, A. 441, 503, 599,
612, 618, 1032
Stecklum, M. 578
Steeghs, N. 608
Steen, B. 266
Steen, I.G. 614
Stegelmann, F. 420
Steger, F. 387, 410, 506
Stegherr, Anna-M. 57
Steidel, C. 637
Steiger, Hans-J. 655, 658, 660
Stein, A. 623, 650
Stein, B. 743
Stein, H. 404
Stein, M. 669
Stein, U. 794, 799, 853
Steinau, Hans-U. 307
Steinau, P. 490
Steinberger, P. 141
Steindorf, K. 138, 256
Steiner, T. 463
Steinert, R. 516, 517
Steinmann, D. 793
Steinmetz, T. 185
Stelz, A. 809
Stengel, A. 431, 699
Stenzinger, A. 374, 409, 520
Stenzl, A. 676
Stephan-Falkenau, S. 190
Sternberg, Cora N. 295
Stevanovic, S. 454
Stickeler, E. 254, 417, 629, 683
Stiller, F. 847
Stingl, J. 382
Stintzing, S. 348, 756
Stobäus, N. 379
Stock, S. 1032
Stöckle, N. 856
Stoecklein, Nikolas H. 849
Stoehr, R. 546
Stögbauer, F. 475
Stohner, M. 223
Stöhr, R. 383, 610, 634
Stoiber, F. 495
Stoiber, S. 1040
Stojanovic, N. 848
Stojnev, S. 543
Stolz, R. 642, 793
Stölzel, F. 462, 609
Stonik, V. 530
Stonik, Valentin A. 326
Storck, L. 251
Stössel, S. 45, 501
Strassmann, D. 782
Stratmann, J. 297
Straub, Lesley-A. 623, 650
Straube, C. 475
Strauß, B. 316, 539
Strauss, Hans G. 576
Strebel, R. 64, 65
Streckmann, F. 294, 313
Streubel, A. 190
Streuer, A. 755
Strick, R. 383
Strik, D. 629
Strissel, P. 383
Strobel, H. 200
Strobel, O. 433
Ströbel, P. 704
Strohmaier, P. 400
Strömsdörfer, J. 157
Stropiep, U. 181, 464
Stull, Dawn M. 804
Sturmheit, T. 551
Stuschke, M. 464, 898, 985
Stutz, U. 73
Suarez-Gosalvez, J. 1040
Subklewe, M. 702
Suckrau, Pia M. 604, 606, 635
Südho, T. 434
Sukhotko, A. 775, 783, 817
Sültmann, H. 374
Sultova, E. 461
Süß, C. 387, 410, 506
Sydow, Saskia R. 635
T
Tabatabai, G. 386, 400, 407, 438,
454, 514, 625, 965
Tabernero, J. 608
Tafel-Stein, E. 574
Takahashi, M. 788
Talazko, J. 769, 834
Tamaskovics, B. 194
Tamm, I. 185
Tammela, T. 249
Tan, Daniel S.W. 274, 402
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 263
Inhalt
2018
Index
2018
Tank, M. 379
Tannapfel, A. 377, 533
Tannir, Nizar M. 132, 323
Taraki, H. 851
Taraki, I. 833
Taran, Florin-A. 215
Tatagiba, M. 400, 438, 514, 965
Taubenhansl, C. 487
Tauber, R. 980
Taubert, H. 383, 546, 610
Taugner, J. 555
Tauscher, M. 432
Tautenhahn, Hans-M. 859, 860, 861
Taylor, K. 570
Tech, S. 426
Telzerow, E. 445
Templin, M. 334, 362
Tenev, V. 1033
Teoman, A. 843
Téoule, P. 981
Terbach, R. 539
Terhardt, D. 112
Terheyden, P. 320, 816
Terpos, E. 804
Tesch, H. 142, 588, 636, 994
Teschendorf, C. 533
Theodoraki, Marie-N. 200, 287, 329
Theodoropoulou, S. 912
Thiede, C. 781
Thiel, F. 523
Thiel, U. 1048
Thieme, R. 759, 800, 802
Thiery-Vuillemin, A. 690
Thies, S. 645
Thiesing, Lisa C. 693
Thiesler, T. 1029
Thiessen, N. 524
Thietje, R. 155
Thill, M. 254
Thimme, R. 739
Thiyagarajah, P. 581
Thode, C. 629
Thoene, S. 475
Thomaidou, D. 993
Thomalla, J. 184
Thomas, M. 125, 201, 374, 393,
394, 395, 409, 484,
520, 652, 672, 934
Thompson, M. 804
Thomsen, A. 187
Thong, M. 106, 281, 289, 792, 803
Thong, Melissa S.Y. 65
Thronicke, A. 680, 894
Thuss-Patience, P. 143, 218, 788
Tibes, R. 1052
Tiburtius, C. 155
Tiebel, O. 781
Tiemann, Maria-L. 335
Tiemann, M. 181, 464, 594
Tiller, U. 649
Timm, B. 276
Tio, J. 160, 814
Tischendorf, L. 29
Tiseo, M. 875
Tjaden, C. 971
Todenhöfer, T. 249
Todorovic, J. 543
Toeper, Anne-M. 408
Toi, M. 167, 328
Tolaney, S. 167, 168, 330
Tolkachev, A. 851
Tolkmitt, M. 547
Tomanek, A. 960
Tomaschko, K. 642
Tomé, O. 684
Tönsing, J. 111
Topper, M. 1032
Torregrosa Diaz, José M. 781
Tortora, G. 822
Tosi, D. 402
Tournigand, C. 1016
Toussaint, F. 889
Träger, W. 124
Traut, A. 265
Treeck, O. 360
Treitschke, S. 848
Trenn, G. 533
Triebel, F. 997
Trillsch, F. 461, 893
Tripon, D. 265
Trojan, J. 223
Trukhin, D. 399
Tschalener, B. 160
Tschuschke, V. 151
Tsiouris, A. 256, 666
Tsuboi, M. 659
Tubío Santamaría, N. 111
Tuchscherer, A. 673
Tuchscherr, L. 492
Tufman, A. 555, 779, 780, 934
Tukmakov, A. 775
Twardowski, P. 690
Twrznik, M. 25
Tzaridis, T. 407
Tzschaschel, M. 215
U
Uckert, W. 467
Uemura, H. 372
Uacker, L. 377, 398
Ugocsai, P. 540, 835, 843, 848
Ugurel-Becker, S. 889
Uhl, W. 455, 533, 646, 854
Uhlig, J. 405
Ukena, D. 591
Ulm, B. 934
Ulrich, J. 320
Ungar, N. 256, 462
Unger, T. 373
Unsöld, L. 125
Untch, M. 142, 232, 588, 629,
636, 683, 694
Urban, D. 659
Urban, L. 1000
Urschitz, M. 941
Ushmorov, A. 200, 287
Usmani, S. 804
Utikal, J. 320, 816
V
Vaccaro, G. 916
Vach, W. 261
Valcheva, V. 172, 174
Valent, P. 742
Valentini, J. 642
Valesky, E. 823
Van Cutsem, E. 608, 822, 916,
1016
van der Heijden, Michel S. 727
van Mackelenbergh, M. 629
van Oorschot, B. 369
van Roye, C. 184
van Tilburg, Cornelis M. 274, 282
Vannier, C. 270, 272, 405
Vänttinen, M. 1040
Vansteene, D. 1053
Vcev, A. 298
Vehling-Kaiser, U. 426, 756
Vela-Ojeda, J. 804
Venerito, M. 172, 174, 918
Verbeke, Caroline S. 433
Verderame, F. 399
Verdoodt, B. 533
Vergnenegre, A. 884, 1008
Vermaelen, K. 1000
Verret, W. 882
Vesper, Anne-S. 598, 814
Vettorazzi, E. 623, 650
Vicente, D. 579
Viciano, Cristina P. 526
Villalobos, M. 125
Villard, C. 433
Villegas, Augusto E. 579
Visseren-Grul, C. 242
Vitinius, F. 1032
Vladimirova, D. 260
Vlasova, M. 817
Vogel, A. 608, 758, 916
Vogt, B. 834
Voiß, P. 494, 793
Voitko, O. 399
Voland, A. 505
Volckmar, Anna-L. 409
Völkel, V. 748, 749, 750,
751, 466
Volkmar, Anna-L. 374
Voltz, R. 56
von Amsberg, G. 326, 530
von Bergwelt-Baildon, M. 445, 687, 761
von Blanckenburg, P. 921
von Bubno, N. 580, 637, 742
von Deimling, A. 86
von der Heyde, E. 259, 324, 391,
395, 472
von der Winkel, G. 316, 539
von Eggeling, F. 317
von Einem, Jobst C. 348, 756
von Falck, C. 563
Von Fritschen, U. 114
von Grundherr, J. 623, 650
von Klot, C. 720
von Laue, Hans B. 311
von Lilienfeld-Toal, M. 302, 647
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Oncol Res Treat 2020;43(suppl 1):1–265 Author Index264
Inhalt
2018
Index
2018
von Luettichau, I. 396
von Lüttichau, I. 968
von Mackelenbergh, M. 814
von Trott, P. 680, 894
Vonnahme, M. 499
Vordermark, D. 414, 441, 503, 544,
583, 599, 612, 618,
692, 723, 998, 1050
Vorholt, D. 255
Vorobyev, N. 833, 851
Voss, M. 993
Vucinic, V. 640, 776, 819
W
Wach, M. 183
Wach, S. 383, 546, 610
Wacker, Frank K. 782, 899
Wacker, H.H. 156
Wadell, T. 1037
Wadsworth, C. 579
Wagner, C. 141
Wagner, H. 238
Wagner, Johannes M. 331
Wagner, K. 261
Wagner, M. 683
Wagner, S. 141
Waha, A. 197
Wahib, R. 551
Waidmann, O. 117, 171
Waldau, A. 486
Waldenberger, D. 259
Waldmann, A. 289, 792, 803
Waldner, M. J. 931
Waldschmidt, D. 404
Walewska, R. 236
Walke, Gerrit-R. 342, 350, 353, 355,
356, 357, 358,
359, 364, 368
Walke, M. 614, 836
Walker, J. 581
Walker, P. 236
Waller, Cornelius F. 393
Walles, T. 301
Wallner, C. 331
Walter, B. 454
Walter, F. 836
Walter, J. 492, 648, 649, 662, 584
Walter, R. 190, 604, 606, 635
Walter, S. 490
Walter-Diessars, M. 648
Walther, W. 794, 853
Wandmacher, Anna M. 149
Wang, M. H. 236, 976
Wanner, M. 64, 65
Wappenschmidt, B. 162, 197, 585
Wardley, A. 330
Warm, Mathias R. 552
Wasan, H. 608
Watzlawik, M. 304
Weber, D. 900
Weber, F. 835
Weber, G. 820
Weber, K. 130, 131, 389
Weber, M. 574, 595, 600
Weber, S. 266
Weber, W. 199
Weber-Lassalle, K. 585
Weber-Lassalle, N. 142, 585
Wedding, U. 369
Wedeken, K. 181, 464
Wege, Anja-K. 153, 540
Wegert, L. 623, 650
Wehler, T. 581, 644
Wehrhan, F. 595, 600
Weibl, K. 776
Weich, C. 449
Weichental, M. 856
Weichenthal, M. 320
Weichert, W. 112, 199, 262, 393,
394, 395, 475, 493,
Weide, R. 184, 185
Weidele, K. 848
Weigel, M. 588
Weigert, M. 288
Weigl, K. 176, 349, 352
Weikert, L. 417
Wein, A. 341
Weinfurtner, N. 519
Weinmann, A. 999
Weis, Cleo-A. 755
Weis, J. 134, 246, 566
Weise, S. 612
Weisel, K. 804
Weishaupt, C. 320
Weiß, D. 310
Weiß, J. 494
Weißbach, J. 589
Weißer, L. 792
Weissinger, Stephanie E. 200, 397
Weller, C. 654
Weller, J. 499 Wellmann, I.
541
Welslau, M. 211, 259, 270,
272, 463, 771, 994
Welt, A. 254, 270, 272
Welzel, G. 708
Wen, X. 884
Wenke, T. 288
Wenzel, C. 771
Wenzler, M. 834
Werner, J. 367
Werner, R. 190
Werno, C. 848
Wesseler, C. 181, 934
Wesselmann, S. 470, 798
Wessolly, M. 190, 604, 606, 635
Westermann, J. 467
Westphalen, B. 428, 461, 687
Westphalen, C. B. 761, 756
Wetzel, N. 426
Weyer, V. 755
Weyerer, V. 383, 546, 610, 634
White, Helen E. 744
Whiteley, J. 581
Wichmann, C. 950
Wichmann, O. 645
Wichmann, Y. 802
Wickert, M. 268
wiedemann, C. 201, 520
Wiedemann, R. 197, 1032
Wiegert, E. 1016
Wiekhorst, F. 809
Wierda, W. 236
Wierick, E. 303
Wieschermann, U 912
Wiese, S. 443
Wiese-Posselt, M. 645
Wiesmüller, E. 772
Wiesmuller, M. 931
Wiest, G. 934
Wiesweg, M. 464
Wiezorek, T. 648, 662
Wijayawardana, S. 167
Wild, P. 223, 501
Wild, Philipp S. 597
Wildenberger, K. 744
Wilhelm, M. 1047
Wilkat, M. 287
Wilke, Anne C. 266
Wille, K. 1051
Willibald, S. 313
Willich, C. 614
Wiltink, J. 666
Wimberger, P. 684, 950
Windisch, P. 37
Wingerter, A. 45, 501
Winkler, M. 793
Winter, C. 475
Winter, H. 409, 672
Winter, L. 708
Wirth, M. 463, 475
Wirtz, M. 119
Wirtz, R. 610, 634
Wirtz, Ralph M. 383, 546
Wirtz, S. 389, 820
Wiskemann, J. 256, 462, 505,
730, 732
Witt, C. 494, 793
Witte, C. 642
Witte, S. 441, 503
Wittekind, C. 452, 476
Wittekindt, C. 259
Wittenborn, J. 417
Wittershagen, S. 1029
Wittig, A. 648, 662
Wittwer, A. 813
Witzens-Harig, M. 115
Wöckel, A. 254
Woehl, M. 148
Woessmer, B. 842
Wohlberedt, K. 528
Wohlschläger, J. 604, 606, 635
Wolf, Hans-H. 529
Wolf, I. 816
Wolf, J. 208, 469, 992, 995
Wolf, S. 266
Wolf, T. 426
Wol, Klaus D. 475
Wol, M. 609
Wol, S. 221, 512
Wolmark, N. 694
Wolters, H. 533
Wong S. 236
Woopen, H. 684
Wörmann, B. 445
Worst, T. 610
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Oncol Res Treat 2020;43(suppl 1):1–265Author Index 265
Inhalt
2018
Index
2018
Worst, Thomas S. 546
Wöstemeier, A. 551
Woyach, J. 236
Wroblewski, M. 484
Wu, C. 995
Wu, S. 644
Wu, W. 690
Wu, Y.-L. 659
Wuchter, P. 115
Wuerein, D. 238
Wulf-Goldenberg, A. 578, 615
Wülng, P. 303
Wullich, B. 383, 546
Wullweber, A. 383
Wunderlich, H. 619
Wunsch, K. 497
Wünsch, A. 235
Wünsch, V. 472
Wunschel, R. 214
Würein, D. 693
Würstlein, R. 461, 687, 771
Wyrich, M. 635
Wyrwa, A. 156
Wyrwich, K. 400
X
Xu, D. 882
Xu, Q. 755
Xyländer, M. 235
Xynos, I. 788
Y
Yaeger, R. 608
Yahiaoui-Doktor, M. 986
Yang, C. 169
Yang, J.C.-H. 875
Yang, L. 582, 628
Yang, Z. 330
Yao, W. 652
Yardley, D. 168
Yau, T. 117, 172
Ye, C. 402, 586
Ye, J. 644, 727
Yen, Chueh-C. 788
Yoh, K. 242
Yomade, O. 156
Yoshino, T. 608
Yu, C.-J. 659
Yuan, Z. 374
Z
Zachariah, R. 816
Zacharias, S. 458
Zadeh, G. 965
Zagonel, V. 117
Zahm, Dirk-M. 636
Zahn, M.-O. 405, 458, 958
Zhu, Andrew 882
Zahn, Mark-O. 254, 303, 393, 426
Zaiss, M. 272, 405
Zakrzewski, F. 288, 641
Zamagni, E. 302
Zambelli, S. 330
Zamzow, P. 580
Zannori, C 1000
Zardo, P. 782
Zavatta, E. 1022
Zblewski, D. 1052
Zeder-Goss, C. 893
Zeißig, S. 289, 792, 803
Zeiler H-J. 914, 950
Zellner, M. 155
Zeman, F. 153
Zemojtel, T. 374
Zengerling, F. 295, 546, 610, 772
Zepp, M. 962, 1033
Zerbes, Ralf M. 276
Zerm, R. 311
Zermann, Dirk-H. 342, 350, 353, 355,
356, 357, 358, 359,
364, 368, 547
Zernecke, A. 526
Zetzl, T. 28
Zeugner, S. 288
Zeuzem, S. 223
Zhan, T. 149
Zhang, K. 372
Zhen, H. 916
Zhang, P. 875
Zhou, C. 607
Ziegler, David S. 282
Ziegler, L. 386
Zielasek, J. 575
Zielke, T. 793
Zielinski, C. 1019
Ziemann, F. 701, 702
Zihler, D. 816
Zikiryahodjaev, A. 775, 783
Zikiryakhodzhaev, A. 817, 829
Zimmer, L. 889
Zimmer, P. 45, 619
Zimmermann, Annamaria H. 242
Zimmermann, J. 199
Zimmermann, T. 93, 231, 237
Zincke, F. 799, 853
Ziouti, F. 188
Zipfel, S. 431, 699
Zipprich, A. 382
Zips, D. 400
Zojer, N. 529
Zonder, J. 804
Zorn, A. 339
Zschäbitz, S. 1037
Zschummel, M. 467
Zsebedits, D. 260
Zurawski, B. 1008
Zürich, A. 641
Zwerenz, R. 666
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